• brain banks;
  • cerebral cortex;
  • neurochemical abnormalities;
  • oxidative stress;
  • Parkinson’s disease;
  • post mortem


  1. Top of page
  2. Abstract
  3. Introduction
  4. Brain banks for PD
  5. Insight into the biochemistry of PD using autopsy material
  6. Concluding remarks
  7. Acknowledgements
  8. References

Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson’s disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field. We emphasize the potentials and pitfalls when using high-quality specimens of the human central nervous system for advancing PD research. PD is a generalized disease in which α-synuclein is not a unique component but, instead, is only one of the players accounting for the complex impairment of biochemical/molecular processes involved in metabolic pathways. This is particularly important in the cerebral cortex, where altered cognition has a complex neurochemical substrate. Mitochondria and energy metabolism impairment, abnormal RNA, microRNA, protein synthesis, post-translational protein modifications and alterations in the lipid composition of membranes and lipid rafts are part of these complementary factors. We have to be alert to the possible pitfalls of each specimen and its suitability for a particular study. Not all samples qualify for the study of DNA, RNA, proteins, post-translational modifications, lipids and metabolomes, although the use of carefully selected samples and appropriate methods minimizes pitfalls and errors and guarantees high-quality reserach.


cerebrospinal fluid


Lewy body


Parkinson’s disease


superoxide dismutase


  1. Top of page
  2. Abstract
  3. Introduction
  4. Brain banks for PD
  5. Insight into the biochemistry of PD using autopsy material
  6. Concluding remarks
  7. Acknowledgements
  8. References

Brain banks are vital in the scientific research of Parkinson’s disease (PD) because they have the facilities and the expertise to recruit, classify, preserve and distribute specimens for research, abiding by the local ethical and legal framework. Because most human neurodegenerative diseases are mainly or only observed in humans, the availability of specimens (i.e. tissues and body fluids) in brain banks and biobanks is a major resource for research. Brain banks have proved to be excellent platforms and vital facilities for improving our understanding of neurological diseases [1–3]. They serve as a central steering unit for the establishment of practical and acceptable ethical guidelines to be followed in the procurement and dissemination of autopsy material for scientific research on PD [4–6].

PD is clinically characterized as a complex motor disorder, as manifested by resting tremor, slowness of initial movement, rigidity and general postural instability, and, pathologically, by a loss of dopaminergic neurones in the substantia nigra pars compacta, leading to reduced dopaminergic input to the striatum, accompanied by adaptative responses in the internal and external globus pallidus, subthalamus, thalamus and substantia nigra pars reticularis. Round, hyaline neuronal cytoplasmic inclusions called Lewy bodies (LBs) and enlarged aberrant neurites and threads, mainly composed of altered α-synuclein, are found in the substantia nigra and other nuclei, such as the locus ceruleus, reticular nuclei of the brain stem and dorsal motor nucleus of the vagus, as well as the basal nucleus of Meynert, the amygdala and the CA2 area of the hippocampus [7].

Techniques such as those related to neuroimaging and the use of tracers have improved our understanding of PD during life, although there is solid and extensive evidence that clinical and pathological studies provide substantial information and useful correlates [8–10]. Furthermore, biochemical studies of post-mortem specimens of PD are a rich source of information when carried out under the appropriate conditions. Post-mortem biospecimens, such as brain tissue, cerebrospinal fluid (CSF) and blood, are also used for biomarker validation in PD [11].

Below, we deal with two aspects of brain banking in PD. The first aspect comprises the management of brain banks and tissue processing, as well as the potentials and pitfalls encountered when using post-mortem biospecimens for research on PD. The second aspect focuses on biochemical alterations in the cerebral cortex in PD compared to age-matched controls, as derived from the study of human post-mortem brains.

Brain banks for PD

  1. Top of page
  2. Abstract
  3. Introduction
  4. Brain banks for PD
  5. Insight into the biochemistry of PD using autopsy material
  6. Concluding remarks
  7. Acknowledgements
  8. References

Standard operating procedures in brain banking

Several general points must be considered in the management of a brain bank. These include:

  •  A well established local donor system of PD subjects and controls in which consent is obtained for the use of specimens for scientific research, as well as access to the medical records of the donors.
  •  Rapid autopsies with a very short post-mortem delay and a fresh dissection; these are a prerequisite for an increasing range of technical procedures and new systems, such as molecular and biochemical studies in PD.
  •  Compatibility of protocols and standard operating procedures for tissue procurement, management, preparation and storage for diagnostics and scientific research.
  •  A generally accepted consensus on the clinical and neuropathological diagnostic criteria in PD.
  •  Quality control of the disseminated samples (pH/agonal state).
  •  Abidance with internationally accepted guidelines for ethical and legal aspects according to the local medico-legal system.
  •  Monitoring of proper safety procedures.

Ethical aspects

The ethical aspects comprise the categories outlined below.

Tissue procurement: issues related to the PD donor programme and informed consent

Written consent of the donor and/of next-of-kin at the time of death or earlier is mandatory for the use of tissues with respect to medical and basic research. Respect for the dignity of human remains must be considered at all times. All staff working with human remains must be properly trained and qualified.

Tissue management: issues related to collection, handling and preservation

All human specimens should be regarded as potentially biohazardous and be handled accordingly by appropriately trained personnel. Specific precautions should be taken against known hazards and general precautions must also be taken against unknown hazards. All clinical documentation and information concerning the tissues should be made available to users as quickly as possible. All individuals potentially exposed to human brain tissues and fluids should be vaccinated against hepatitis B virus and also be regularly checked for levels of immunity. All disposable equipment used in conjunction with human brain tissues and fluids should be sterilized in accordance with a recommended procedure before transport for incineration. Special care must be taken in cases of acute or subacute dementia (i.e. dementia rapidly developing in a few weeks) because Creutztfeldt–Jakob disease must be considered as a possible cause of the disease. Currently, all brain banks have strict safety management protocols for tissue/body fluid safe handling, aiming to protect against contamination with transmissible agents such as Creutztfeldt–Jakob disease.

Tissue dissemination: factors related to supplying samples of high scientific quality

Users of the brain samples should undergo a process of accreditation to ensure that a minimum set of criteria is fulfilled. These criteria include scientific reputation, ethical credibility, proper training, suitable facilities for safe handling and the disposal of human specimens, as well as confidentiality. Whenever possible, this accreditation should be performed by an appropriately qualified and independent expert group. Because the legislation and documentation concerning shipment of human specimens varies between the European countries, information regarding packing regulations and the national and international transport of human brain tissues and fluids should be made available to all parties involved in brain bank activities for research.


The anonymity of samples and the donor’s identity and records should be protected at all times. Samples supplied for research on PD should be coded by the brain bank and a tissue tracking system restricted to local brain banks must be established to guarantee the anonymity of the donor.

Financial gain

From a legal and ethical point of view, it is highly important to establish brain banks as nonprofit sources of human tissues for scientific research. Brain banks act as a custodian of brain tissue and the tissues must not be handled commercially. On the other hand, it is extremely important to have a reasonable coverage for the costs involved with respect to procurement, handling and transport. All technical and scientific activities and expenses related to the handling and management of tissues, as well as the costs involved in the acquisition and/or preservation of the tissues, can be considered as a budget that must be paid when tissues are requested for research. The various professionals who are involved in obtaining, handling and diagnosing the tissues have the right to be reimbursed for their services. It must be made clear when writing to all users that any possible payments are only made to cover the costs of brain banks, which are forbidden to make any financial profit.

Genetic testing

Research using PD specimens can bring new information about the donor that is also relevant to his/her family. This option should play an important role with respect to ethical conduct. Sometimes there is concern about the need for knowledge and information on the one hand and the use and implications of this information for the individuals involved. The link found between certain genes and PD creates a heavy burden on physicians, healthcare workers and brain bankers who test for these genetic factors because they are essential for diagnostics and the scientific interpretation of results obtained from the specimens. This knowledge poses many difficult questions relating to concerned or afflicted individuals.

When applying for local ethics approval for PD research, care must be taken to include permission not only for diagnostic purposes, but also for the use of tissue in research projects, as well as for shipment of specimens to other laboratories. Permission must also include the use of (anonymized) clinical data and DNA for PD research.

Processing and storage of human post-mortem biospecimens for PD research

The brain is removed from the skull in accordance with well-established protocols, taking special care not to damage the optic nerves, olfactory bulbs and tracts, as well as the superior part of the cervical spinal cord [12]. CSF can be obtained from the third ventricle or the lateral ventricles, avoiding blood contamination that would ruin further studies. The fresh brain must be weighed and the pH of the brain measured in fresh tissue or CSF [13]. The spinal cord is also totally removed along its axis after opening the anterior part of the vertebral column. Spinal ganglia and anterior and posterior nerve roots should be removed carefully. The brain is usually cut in the middle sagittal plane and the two cerebral hemispheres are separated. Alternatively, the cerebrum is separated from the brain stem above the superior colliculi, the cerebellum is separated from the brain stem by cutting the cerebellar peduncles, and the cerebellum is divided by the vermis. One cerebral hemisphere is used for biochemical studies and the other is immersed in 4% buffered formalin for morphological studies. The brain stem and cerebellum are processed either by selecting alternate sections for biochemistry and morphology or by choosing one half for biochemical studies and the other half for morphology. The spinal cord is cut on transversal sections and alternate sections are processed for biochemistry and morphology. For biochemical studies, the fresh brain is cut into coronal sections, 8–10 mm thick. Then, specific areas (approximately 2 mm in thickness) of the cerebral cortex, thalamus, striatum, nucleus basalis of Meynert and amygdala are rapidly dissected. In addition, specific areas and samples of the brain stem, cerebellum, spinal cord, spinal ganglia, spinal roots, olfactory bulb, choroid plexus and hypophysis are processed in the same way. Samples should be frozen on metal plaques over dry ice, kept in individual air-tight plastic bags and numbered with water-resistant ink or by using appropriate tags. The rest of the fresh cerebrum and cerebellum is frozen in coronal sections, packed in individual plastic bags, labelled and stored at −80 °C. Thawing and refreezing should be avoided at all times.

The neuropathological diagnosis is carried out on formalin-fixed, paraffin-embedded samples, sectioned with a microtome and then the tissue sections are processed in accordance with well-established neuropathological and immunohistochemical protocols. Tissue blocks are always stored for additional studies.

Cryoprotected samples and samples processed for electron microscopy can be obtained in most brain banks. Preservation of CSF and serum is conducted by rapid freezing and storage at −80 °C. DNA must be obtained by appropriate methods and stored at −80 °C. RNA from the peripheral blood is usually obtained after collecting peripheral blood in special tubes and processing the lysates for RNA extraction. Specimens from PD donors and controls are properly matched for various ante- and post-mortem factors.

General limitations and putative pitfalls in biochemical and molecular studies of post-mortem specimens

Ante-mortem factors include agonal state, hypoxia, acidosis, fever, seizures and medication used. Post-mortem factors include the post-mortem delay or interval (i.e. interval between death and sample processing), temperature of the body, type of fixative, duration of fixation/storage and the processing of frozen material [13]. A third group of factors appear to be unpredictable, such as those related to individual variations between cases subjected to similar pre-mortem and post-mortem conditions, as well as those related to regional differences within the same individual [14].


Fresh frozen material, even when stored for years, is suitable for DNA studies. However, DNA is vulnerable to degradation in liquid solutions, particularly those fixatives used for tissue preservation in current pathological practice. Sub-optimal DNA preservation or even massive degradation is found in tissues stored in formalin at room temperature for several months or years. DNA quality may be sub-optimal or bad in samples taken from paraffin blocks produced several months or years after fixation. Gene methylation is not altered with a short post-mortem delay in frozen samples, yet histone tail acetylation is markedly affected by a post-mortem delay in a very unpredictable manner. Acetylation may increase shortly after post-mortem and then decrease, thus mimicking the responses observed in the penumbra area of infarctions. Because the responses vary from one individual to another and also from one acetylation site to another, comparative studies of histone tail acetylation in post-mortem brains are largely imprecise.


RNA integrity is largely dependent on several factors mainly related to the agonic state and is variable from one region of the brain to another, with little possibility of prediction. For this reason, each sample, even when obtained from the same brain, has to be analyzed separately for RNA preservation. Moreover, the use of agarose gels to reveal RNA integrity is nonprecise, and the use of bionalyzers (e.g. BioAgilent 2100 Bioanalyzer; Agilent Technologies Inc., Santa Clara, CA, USA) is compulsory when aiming to avoid studying samples with low RNA integrity number values. Another point worthy of note is the selection of appropriate house-keeping genes for normalization because some of them (albeit stable under normal conditions) can be targets of neurodegeneration. Consequently, a preliminary selection of genes that are not modified should be characterized in the study of a particular disease. Small RNAs appear to be more resistant than mRNAs, although special care must be taken to reproduce the results in different cases as a form of validation for individual observations.


The effects of post-mortem delay on protein preservation depend largely on the temperature of storage, as well as the vulnerability of individual proteins to post-mortem delay and the state of the protein. For practical purposes, the screening of a particular antibody recognizing a specific protein should be tested under conditions mimicking an artificial post-mortem delay aiming to identify a decline in the expression of the particular protein and, therefore, to establish the appropriate range of post-mortem delay times for the study of the specific samples. This aspect is crucial when using densitometric quantification of the signals after gel electrophoresis and western blotting, and also when using proteomics.

Examination of post-translational modifications must be performed with caution. For example, redox proteomics is a useful tool for identifying proteins damaged by oxidation and nitration. However, oxidative/nitrosative damage may be modified with the agonal state and post-mortem delay. Oxidation and nitration may increase with the agonal state, although oxidative stress markers also decrease with post-mortem delay. Attention to the agonal state and post-mortem parameters (e.g. pH of the CSF or the fresh brain) is mandatory when controlling for artefacts related to post-mortem samples.

Because enzymatic studies and metabolomics largely depend on the preservation of the tissue, and particularly the proteins, it is sensible to first study the profile of degradation with the post-mortem delay of the corresponding proteins.

Insight into the biochemistry of PD using autopsy material

  1. Top of page
  2. Abstract
  3. Introduction
  4. Brain banks for PD
  5. Insight into the biochemistry of PD using autopsy material
  6. Concluding remarks
  7. Acknowledgements
  8. References

PD is a multisystemic disease of the nervous system

James Parkinson described the disease in 1817 with the term shaking palsy. In 1920, Frederick Lewy described the typical neuronal inclusions, later named Lewy bodies. Konstatin Tretiakoff (in 1919) and Rolf Hassler (in 1938) established that the substantia nigra was the main cerebral area affected. In 1950, Arvid Carlsson identified dopamine as the major biochemical defect in the substantia nigra and causative of the dopaminergic denervation of the basal ganglia. The first trials with levo-dopa were carried out in 1967–1968.

The discovery of dopamine defects and the therapeutic effects of dopa or agonists have been central to our understanding and treatment of major motor symptoms (parkinsonian symptoms) in PD. Pioneering and subsequent studies support the importance of molecular and biochemical studies of the brain in human neurodegenerative diseases.

However, PD is not simply a motor disorder. Rather, olfactory dysfunction, dysautonomia, sleep fragmentation, rapid eye movement behaviour disorder, mood and anxiety disorders, and depression are common in PD; these alterations may precede parkinsonian symptoms and they usually increase in intensity with the progression of the disease. Changes in personality and moderate or mild cognitive debilitation are found in PD. Neuropsychiatric alterations and cognitive decline may occur at early stages of parkinsonism, suggesting that they are an integral part of PD from the beginning of the disease in some patients. Characteristically, symptoms are often subtle at the beginning and difficult to detect without neuropsychological tests, although they become aggravated with the progression of the disease. Deficits mainly affect executive function, including working memory and visuospatial capacity.

A correlation between non-motor alterations and neuropathological substrates has been established using several instrumental classifications of LB pathology that help to explain the progression from the medulla oblongata (and olfactory bulb) to the midbrain, diencephalic nuclei and neocortex [15]. Stage 1 is characterized by LBs and neurites in the dorsal IX/X motor nuclei and/or intermediate reticular zone; there is also myentheric plexus involvement. Stage 2 affects the medulla oblongata and pontine tegmentum and covers the pathology of stage 1 plus lesions in the caudal raphe nuclei, gigantocellular reticular nucleus and ceruleus–subceruleus complex; the olfactory bulb is also involved. Stage 3 refers to the pathology of stage 2 plus midbrain lesions, particularly in the pars compacta of the substantia nigra. Stage 4 includes basal prosencephalon and mesocortex pathology (i.e. cortical involvement confined to the transentorhinal region and allocortex, and CA2 plexus) in addition to lesions in the midbrain, pons and medulla oblongata. Stage 5 extends to sensory association areas of the neocortex and prefrontal neocortex. In addition, stage 6 includes lesions in first-order sensory association areas of the neocortex and pre-motor areas; occasionally, there are also mild changes in primary sensory areas and the primary motor field.

The involvement of distinct areas and regions of the central, peripheral and autonomous nervous system indicates that PD is a multisystemic disease of the nervous system. Although several atypical cases (approximately 30%) do not follow a clear gradient of LB pathology from the medulla oblongata to the neocortex, Braak classification has been useful for proposing an instrumental approach that suggests spread or progression of the disease in most cases.

An important point is that motor symptoms and certain non-motor symptoms correlate with LB pathology at specific regions of the peripheral and central nervous system, whereas others do not. As a paradigm of this assertion, cognitive impairment and dementia in PD barely correlate with LB pathology in the cerebral cortex [16], thus inferring that other factors, in addition to altered α-synuclein, probably play key roles in their pathogenesis.

On the other hand, cases with LB pathology in the brain stem without parkinsonism are considered as incidental PD or pre-motor PD [17–19]. Recent studies have shown biochemical alterations in various regions of the nervous system even at these very early stages of the disease.

Taken together, these observations suggest that biochemical rather than morphological studies represent an appropriate approach for increasing our understanding of the molecular pathology of non-motor symptoms in PD.

Below, we report information obtained from the biochemical and molecular studies of human autopsy samples stored in brain banks focused on the cerebral cortex in PD.

Neurochemical alterations related to cognitive impairment in PD

Studies in recent years have changed our understanding of the many mechanisms involved in the deterioration of cognition in PD. On the one hand, neuroimaging studies have shown altered dopaminergic, serotoninergic, cholinergic and noradrenergic innervation of the cerebral cortex, thus providing robust information related to impaired cortical inputs representing major deficits in cortical function. On the other hand, evidence is available showing intrinsic abnormalities in the cerebral cortex in PD even at pre-motor stages of the disease when the brains are analyzed at post-mortem using appropriate methods [20].

Intrinsic cortical alterations are summarized below.

Mitochondria and energy machinery failure

Mitochondria and energy machinery failure are well-known abnormalities in the substantia nigra in PD, and the mutation of several genes encoding proteins related to the mitochondria is causative of familial PD. Recent biochemical studies have revealed mitochondrial abnormalities in the cerebral cortex as well, including decreased brain cortex and mitochondrial O2 uptake and reduced complex I activity in PD. This is accompanied by a higher mitochondrial nitric oxide synthase activity, cytochrome content, expression of superoxide dismutase (SOD)2 and oxidative damage in PD compared to age-matched controls [21].

Increased oxidative damage has been detected in the frontal cortex in PD, in addition to that reported several years ago in the substantia nigra. Redox proteomics has been useful for identifying protein targets of oxidative damage in aged control and diseased brains [22]. Several proteins are targets of oxidative damage in the frontal cortex even at very early stages of PD-related pathology, including α-synuclein, β-synuclein and SOD2 [23,24]. Other relevant proteins are also oxidatively damaged in PD: UCHL1, SOD1 and DJ-1 [25–27]. In addition, increased oxidative damage to aldolase A, enolase 1 and glyceraldehyde-3 phosphate dehydrogenase, which are all involved in glycolysis and energy metabolism, is found in the frontal cortex in pre-motor stages of PD and in established parkinsonian PD [28].

Altered mRNA expression

Altered mRNA expression has been reported in the posterior cingulate cortex in PD compared to age-matched controls, and this increases in PD cases with dementia [29]. An interesting point is the observation of down-regulation of numerous genes involved in mRNA splicing, thereby implicating alterations in mRNA processing in the pathogenesis of dementia in PD [29]. mRNA expression in the cerebral cortex differs in PD compared to Alzheimer’s disease, thus indicating disease-specific modifications in gene expression [30].

Abnormal microRNA down-regulation

Abnormal microRNA miR34b and miR34c down-regulation has been described in the amygdala, substantia nigra, frontal cortex and cerebellum in PD. Down-regulation of miR-34b or miR-34c in differentiated SH-SY5Y dopaminergic neuronal cells results in a moderate decrease in cell viability that is accompanied by altered mitochondrial function and dynamics, oxidative stress, and a decrease in total cellular ATP content. This is accompanied by decreased DJ1 and parkin expression. These findings support the notion that deregulation of miR-34b/c in PD triggers downstream transcriptome alterations underlying mitochondrial dysfunction and down-regulation of DJ1 and parkin in PD [31].

Altered protein expression in neocortex

Proteomics using bidimensional gels in post-mortem brain samples is still subject to validation by other methods [32]. However, precise results have been obtained using subcellular fractionation, such as after the isolation of midbrain and cortical LBs. Research on protein expression in the neocortex in PD is limited [33,34]. In one of these studies, mortalin, a mitochondrial protein also named mitochondrial heat shock protein-70, was found to be decreased with progression of the disease in the cerebral cortex in PD [35], corroborating earlier observations of mortalin alteration in the substantia nigra in PD, and supporting the involvement of mortalin in the progression of PD [35]. This is an important point because mortalin maintains mitochondrial homeostasis, antagonizes oxidative stress damage, interacts with several damaged proteins and cooperates with PD-linked proteins as parkin in mitochondrial function [36].

Interestingly, glutathione S-transferase pi, which is involved in the regulation of oxidative stress, is also dysregulated in the cerebral cortex with progression of the disease in PD [33].

Lipid composition is altered in total membranes and in lipid rafts

Abnormal lipid composition occurs in the frontal cortex at very early stages of PD-related pathology, with significantly increased expression levels of the highly peroxidizable docosahexanoic acid and an increased peroxidability index [23]. Altered lipid composition is particularly marked in lipid rafts in which dramatic reductions are seen in n-3 and n-6 long chain polyunsaturated fatty acid content, mainly docosahexaenoic acid and arachidonic acid, as well as increased medium- and long-chain saturated fatty acids compared to control brains, thus leading to increased membrane viscosity and most likely increased oxidative stress [37].

Impaired cortical metabolism

Impaired cortical metabolism has also been supported using other methods. Cerebral glucose metabolism is reduced in the cerebral cortex in PD patients suffering from cognitive impairment [38–41]. Longitudinal studies have shown that idiopatic PD is accompanied by decreased metabolism in selected cortical areas and that the progression of dementia in the same series of cases was associated with mixed subcortical and cortical deficits [42].

Abnormal proteins at the synapses

Abnormal proteins at the synapses may account for the altered cortical function observed in PD. Tau phosphorylation and α-synuclein phosphorylation are increased in synaptic-enriched fractions of frontal cortex homogenates in PD in the absence of LBs in the same tissue samples [43]. This indicates that there are early α-synuclein alterations at the synapse even in cases with no cognitive impairment [44]. Recent observations have further demonstrated the presence of small abnormal aggregates of α-synuclein at the synapses [44,45]. It is worth emphasizing that altered α-synuclein may result in altered protein–protein interactions, leading to altered synaptic function. Thus, abnormal interactions have been reported between α-synuclein and Rab3a, a protein involved in synaptic vesicle trafficking; Rab5, a protein involved in dopamine endocytosis; and Rab8, a protein engaged in transport [46].

Concluding remarks

  1. Top of page
  2. Abstract
  3. Introduction
  4. Brain banks for PD
  5. Insight into the biochemistry of PD using autopsy material
  6. Concluding remarks
  7. Acknowledgements
  8. References

The first part of this review highlights the key role that brain banks play in collecting and providing samples for PD research. Interpretation of the research results must be conducted with great care to exclude the confounding factors resulting from heterogeneity of the material with respect to the various factors noted previously. Because both animal and cellular models of PD [47,48] are unable to explain all the biochemical pathways and changes specific to PD in humans, the availability of specimens from deceased PD donors and normal controls, whether fresh, frozen or fixed, facilitates and catalyzes the development of methodologies for studying the neurochemical aspects of the disease. Currently, it is possible to correlate functional changes with neurochemical and neuroanatomical changes. Knowledge that certain compounds and structures in the human brain become irreversibly damaged within seconds or minutes after death has led to the widespread idea that autopsy material is unsuitable for research purposes and is unable to provide answers to the various fundamental questions about processes occurring in normal or diseased brains. However, an overwhelming amount of published data obtained using post-mortem material shows that this is a misconception.

The second part of the review reports recent findings confirming that the proper application of techniques in optimally-preserved autopsy specimens offers unique opportunities for biochemical and molecular research in PD. Perhaps with the exception of histone tail acetylation studies, other events can be examined in detail when selecting appropriate samples. Methylation of gene promoters, DNA studies, DNA binding, mRNA expression, study of microRNAs (and probably other small RNAs), proteins, post-translational modifications (even those related to oxidative and nitrosative damage), lipid composition in total homogenates and lipid rafts, enzymatic assays and analysis of the metabolomes have all been successfully assayed in PD.

Multiple pieces of the extremely complex puzzle are still missing, and comprehensive multidisciplinary and multimethodological studies are needed to unveil pathogenic mechanisms of non-motor alterations in PD.

Finally, we would like to stress the need for a close collaboration between brain banks and scientists who are focused on basic research. We have learnt over the years that autopsy specimens are subject to deterioration mainly as a result if pre-mortem (agonal state, infection, fever, convulsions) and post-mortem delay factors (time, temperature). The application of rapid autopsies with a short post-mortem delay and the use of fresh dissection procedures in combination with optimized standard operating procedures are vital for avoiding pitfalls and artefacts and guarantee high-quality research on PD.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Brain banks for PD
  5. Insight into the biochemistry of PD using autopsy material
  6. Concluding remarks
  7. Acknowledgements
  8. References

Work carried out at the INP (I.F.) and used in the preparation of the manuscript was supported by BrainNet II: European network of brain banks EU 2004-CT-2004-503039, INDABIP LSHM-CT-2006-037050 Molecular Diagnostics and FIS grant PI1100968. We wish to thank T. Yohannan for providing editorial assistance.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Brain banks for PD
  5. Insight into the biochemistry of PD using autopsy material
  6. Concluding remarks
  7. Acknowledgements
  8. References
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