title: Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mitchell
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Cochran
authors.forename: Jonathan
authors.initials: J
authors.lastname: Nissanov
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Han
authors.forename: Julia L
authors.initials: JL
authors.lastname: Bienias
authors.forename: Virginia M -Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000401:mortality / Q000473:pathology*; D003072:Cognition Disorders / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000473:pathology; D020534:Parahippocampal Gyrus / Q000473:pathology*; D011446:Prospective Studies; D016875:tau Proteins / Q000032:analysis* / Q000378:metabolism
chemical_list: D016875:tau Proteins