At the 50th Anniversary of the Japanese Society of Neuropathology, I (KK) was requested to present our first DLBD case1 showing progressive dementia and parkinsonism, which we had reported in Acta Neuropathologica in 1976. I had been the patient's attending physician when she was admitted to our hospital. At that time, she had already become severely demented and had marked parkinsonism. I clinically diagnosed the patient as having AD. At that time, it had been thought that both AD and Pick's disease were rare in Japan. Neuropathologically the findings were compatible with AD and PD. In addition, I found many eosinophilic inclusion bodies in small neurons of the deeper layers of the cerebral cortex. Then, I wondered what these bodies were. Prior to that time, it was thought that Lewy bodies only rarely occurred in the cerebral cortex.
Thereafter, I also found many similar cortical eosinophilic bodies in the brain of another patient2 with similar clinical symptoms. I became interested in these cortical eosinophilic bodies. Morphologically these bodies were similar to, but somewhat different from, brain stem Lewy bodies. Therefore, I could not identify these cortical eosinophilic bodies as Lewy bodies. Based on histochemical and electron microscopic examinations, I demonstrated that these cortical eosinophilic bodies were cortical Lewy bodies. In 1978, we reported a second paper2“Lewy bodies in cerebral cortex” in Acta Neuropathologica, based on our three cases including the first case. In that report, the close relationship between cortical Lewy bodies and neuronal cell death was for the first time indicated by showing six developmental stages of cortical Lewy bodies. In addition, we pointed out for the first time that the amygdala and claustrum are also predilection sites for Lewy bodies. Following these papers, some similar cases were reported in Japan. In the USA, a Japanese neuropathologist, Okazaki, and his colleagues5 reported two similar American autopsied cases without Alzheimer pathology in 1961, but these cases had not received attention until our citation of their paper in our first paper.1 In addition, Forno et al.6 also reported a similar American case in 1978. In 1979, we reported3 two similar German cases when I was at the Max-Planck Institute of Psychiatry in Munich. These were the first DLBD cases reported in Europe. In 1984, we proposed4 the term “diffuse Lewy body disease (DLBD)” based on our 11 autopsies including Japanese, German and Austrian cases. As we proposed it in 1980, 11 DLBD was thought to be a type of “Lewy body disease”. We classified Lewy body disease into three types: brainstem type, traditional type and diffuse type. The diffuse type is now considered DLBD, while the brain stem type is considered PD. After our proposal of DLBD in 1984, this disease received more attention among European and American researchers. In 1990, I reviewed 37 autopsied DLBD cases reported in Japan.9 Then I classified these cases into two forms: a common form with a more or less Alzheimer pathology, and a pure form without such findings. In addition, I pointed out that the clinical features differed between the two forms. In the common form, all cases showed presenile or senile onset, and the chief clinical feature was progressive dementia, followed by parkinsonism in 70% of cases, while in the pure form most cases showed early onset and the chief clinical symptom was parkinsonism, followed by dementia. In 1993, when I was invited to the 150th Anniversary of the German Psychiatry Association, I presented the clinical differences between Japanese and Euro-American cases of DLBD12. In the common form, there was no difference between the two, while in the pure form, Japanese cases were usually of young onset with parkinsonism as the chief symptom and Euro-American cases were of older onset with progressive dementia as the chief symptom, similar to the common form. Around that time, the term “senile dementia of Lewy body type” was proposed by Perry et al.,13 and the term “Lewy body variant of Alzheimer's disease by Hansen et al.14 in 1990. In 1995, the first International Workshop7 was held in Newcastle-upon-Tyne, UK. Then, the term “dementia with Lewy bodies” (DLB) was proposed, and the clinical and pathological diagnostic criteria (Consortium on Dementia with Lewey Bodies guidelines)8 were published in Neurology in 1996. In 1996, we proposed the cerebral type of Lewy body disease,15 in which progressive dementia without parkinsonism was the main symptom, and cortical Lewy bodies were marked in the cerebral cortex, but only rare Lewy bodies were present in the brain stem. The presence of the cerebral type means that Lewy bodies could occur first in the cerebral cortex and later develop in the brain stem.
As above-mentioned, we proposed the term Lewy body disease in 1980,11 and since then, we have insisted that DLB(D), PD, and Parkinson's disease with dementia (PDD) should be understood within the spectrum of Lewy body disease.16 This insistence has been recently accepted by the International Workshop and the International Working Group on DLB and PDD in 200517 and in 2006,18 respectively.
In 1997, two very important findings were reported. Polymeropoulas et al.19 reported the mutation of the alpha-synuclein gene in familial PD, and Spillantini et al.20 reported alpha-synuclein in Lewy bodies. Since then, alpha-synuclein has received attention in neuropathological and molecular biological studies.
Our alpha-synuclein immunohistochemical examination of materials from the first DLBD case disclosed much more marked Lewy pathology in the cerebral cortex than we had expected. Only this Lewy pathology could explain the profound dementia in this case. In addition, this case also had both PD and AD. Therefore, the case is now diagnosed as having a common form9 (especially AD form10) of DLB(D).