Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease

Authors

  • Thomas W. Mitchell VMD, PhD,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA
    Search for more papers by this author
  • Elliott J. Mufson PhD,

    1. Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL
    Search for more papers by this author
  • Julie A. Schneider MD,

    1. Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL
    Search for more papers by this author
  • Elizabeth J. Cochran MD,

    1. Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL
    Search for more papers by this author
  • Jonathan Nissanov PhD,

    1. Computer Vision Laboratory for Vertebrate Brain Mapping, Department of Neurobiology and Anatomy, MCP Hahnemann University, Philadelphia, PA
    Search for more papers by this author
  • Li-Ying Han,

    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA
    Search for more papers by this author
  • Julia L. Bienias ScD,

    1. Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL
    2. Department of Internal Medicine, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL
    Search for more papers by this author
  • Virginia M.-Y. Lee PhD,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    Search for more papers by this author
  • John Q. Trojanowski MD, PhD,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    Search for more papers by this author
  • David A. Bennett MD,

    1. Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL
    Search for more papers by this author
  • Steven E. Arnold MD

    Corresponding author
    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    • Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, 142 Clinical Research Bldg., 415 Curie Blvd., Philadelphia, PA 19104
    Search for more papers by this author

Abstract

Abnormally phosphorylated tau accumulates as neurofibrillary tangles and neuropil threads in older persons with and without Alzheimer's disease. The relationship between neurofibrillary tangles and neuropil threads and how they relate to cognitive function is unknown. This study investigated the relationship between phosphorylated tau lesions and cognitive function in 31 persons participating in the Religious Orders Study, a prospective, longitudinal clinicopathological study of aging and Alzheimer's disease. All subjects underwent detailed neuropsychological performance testing within a year of death and evidenced a spectrum of cognitive performance ranging from normal abilities to mild dementia. Measures of neurofibrillary tangle density and phosphorylated tau immunoreactive structures (predominantly neuropil threads) in the entorhinal and perirhinal cortices by quantitative image analysis were significantly correlated (r = 0.5). In multiple linear regression analyses controlling for age, sex, and education, parahippocampal neurofibrillary tangles and neuropil threads were significantly lower in persons without cognitive impairment compared to those with mild cognitive impairment and/or Alzheimer's disease. Further, neurofibrillary tangles were significantly correlated to measures of episodic memory but not other cognitive abilities; neuropil tangles were not significantly related to memory or other cognitive functions. These data indicate that phosphorylated tau pathology in the ventromedial temporal lobe develop prior to the onset of clinical dementia and their presence is associated with cognitive impairment, particularly impairment of episodic memory.

Ancillary