Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer's disease

Nupur Ghoshal, Francisco García-Sierra, Joanne Wuu, Sue Leurgans, David A. Bennett, Robert W. Berry, Lester I. Binder

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

A multitiered strategy was adopted to assess tau conformational changes within fibrillar lesions during the progression of Alzheimer's disease (AD). Anti-tau monoclonal antibodies whose epitopes are distributed across much of the molecule were used to probe vulnerable brain regions in 37 clinically staged cases obtained from the Religious Orders Study. In this way, tau conformational changes were evaluated as the disease progressed from early cognitive decline to AD. These analyses revealed three main findings. First, the presence of granulovacuolar and fibrillar lesions correlates with several measures of episodic memory, suggesting that these lesions significantly contribute to cognitive dysfunction. Second, neuropil threads precede the appearance of neurofibrillary tangles that in turn precede the appearance of neuritic plaques. Third, tau structural changes, or "conformational signatures," emerged as a result of in situ reactivity to a subset of antibodies and nonreactivity to others, thereby reflecting the underlying status of the tau molecule within the fibrillar lesions. These signatures allowed us to document a sequence of tau conformational changes that occur during AD and to correlate these changes with episodic memory deficits. Furthermore, we were able to compare conformational signatures of tau among different lesion types and determine that the molecular profile of tau is lesion-specific.

Original languageEnglish
Pages (from-to)475-493
Number of pages19
JournalExperimental Neurology
Volume177
Issue number2
DOIs
StatePublished - Dec 2 2002
Externally publishedYes

Fingerprint

Episodic Memory
Alzheimer Disease
Neuropil Threads
Neurofibrillary Tangles
Amyloid Plaques
Memory Disorders
Epitopes
Monoclonal Antibodies
Antibodies
Brain
Cognitive Dysfunction

Keywords

  • Alzheimer's disease
  • Antibody
  • Conformation
  • Episodic memory
  • Epitope
  • Tau

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer's disease. / Ghoshal, Nupur; García-Sierra, Francisco; Wuu, Joanne; Leurgans, Sue; Bennett, David A.; Berry, Robert W.; Binder, Lester I.

In: Experimental Neurology, Vol. 177, No. 2, 02.12.2002, p. 475-493.

Research output: Contribution to journalArticle

Ghoshal, Nupur ; García-Sierra, Francisco ; Wuu, Joanne ; Leurgans, Sue ; Bennett, David A. ; Berry, Robert W. ; Binder, Lester I. / Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer's disease. In: Experimental Neurology. 2002 ; Vol. 177, No. 2. pp. 475-493.
@article{0acaef2cd98e4d68a87789c3203eb9ab,
title = "Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer's disease",
abstract = "A multitiered strategy was adopted to assess tau conformational changes within fibrillar lesions during the progression of Alzheimer's disease (AD). Anti-tau monoclonal antibodies whose epitopes are distributed across much of the molecule were used to probe vulnerable brain regions in 37 clinically staged cases obtained from the Religious Orders Study. In this way, tau conformational changes were evaluated as the disease progressed from early cognitive decline to AD. These analyses revealed three main findings. First, the presence of granulovacuolar and fibrillar lesions correlates with several measures of episodic memory, suggesting that these lesions significantly contribute to cognitive dysfunction. Second, neuropil threads precede the appearance of neurofibrillary tangles that in turn precede the appearance of neuritic plaques. Third, tau structural changes, or {"}conformational signatures,{"} emerged as a result of in situ reactivity to a subset of antibodies and nonreactivity to others, thereby reflecting the underlying status of the tau molecule within the fibrillar lesions. These signatures allowed us to document a sequence of tau conformational changes that occur during AD and to correlate these changes with episodic memory deficits. Furthermore, we were able to compare conformational signatures of tau among different lesion types and determine that the molecular profile of tau is lesion-specific.",
keywords = "Alzheimer's disease, Antibody, Conformation, Episodic memory, Epitope, Tau",
author = "Nupur Ghoshal and Francisco Garc{\'i}a-Sierra and Joanne Wuu and Sue Leurgans and Bennett, {David A.} and Berry, {Robert W.} and Binder, {Lester I.}",
year = "2002",
month = "12",
day = "2",
doi = "10.1006/exnr.2002.8014",
language = "English",
volume = "177",
pages = "475--493",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer's disease

AU - Ghoshal, Nupur

AU - García-Sierra, Francisco

AU - Wuu, Joanne

AU - Leurgans, Sue

AU - Bennett, David A.

AU - Berry, Robert W.

AU - Binder, Lester I.

PY - 2002/12/2

Y1 - 2002/12/2

N2 - A multitiered strategy was adopted to assess tau conformational changes within fibrillar lesions during the progression of Alzheimer's disease (AD). Anti-tau monoclonal antibodies whose epitopes are distributed across much of the molecule were used to probe vulnerable brain regions in 37 clinically staged cases obtained from the Religious Orders Study. In this way, tau conformational changes were evaluated as the disease progressed from early cognitive decline to AD. These analyses revealed three main findings. First, the presence of granulovacuolar and fibrillar lesions correlates with several measures of episodic memory, suggesting that these lesions significantly contribute to cognitive dysfunction. Second, neuropil threads precede the appearance of neurofibrillary tangles that in turn precede the appearance of neuritic plaques. Third, tau structural changes, or "conformational signatures," emerged as a result of in situ reactivity to a subset of antibodies and nonreactivity to others, thereby reflecting the underlying status of the tau molecule within the fibrillar lesions. These signatures allowed us to document a sequence of tau conformational changes that occur during AD and to correlate these changes with episodic memory deficits. Furthermore, we were able to compare conformational signatures of tau among different lesion types and determine that the molecular profile of tau is lesion-specific.

AB - A multitiered strategy was adopted to assess tau conformational changes within fibrillar lesions during the progression of Alzheimer's disease (AD). Anti-tau monoclonal antibodies whose epitopes are distributed across much of the molecule were used to probe vulnerable brain regions in 37 clinically staged cases obtained from the Religious Orders Study. In this way, tau conformational changes were evaluated as the disease progressed from early cognitive decline to AD. These analyses revealed three main findings. First, the presence of granulovacuolar and fibrillar lesions correlates with several measures of episodic memory, suggesting that these lesions significantly contribute to cognitive dysfunction. Second, neuropil threads precede the appearance of neurofibrillary tangles that in turn precede the appearance of neuritic plaques. Third, tau structural changes, or "conformational signatures," emerged as a result of in situ reactivity to a subset of antibodies and nonreactivity to others, thereby reflecting the underlying status of the tau molecule within the fibrillar lesions. These signatures allowed us to document a sequence of tau conformational changes that occur during AD and to correlate these changes with episodic memory deficits. Furthermore, we were able to compare conformational signatures of tau among different lesion types and determine that the molecular profile of tau is lesion-specific.

KW - Alzheimer's disease

KW - Antibody

KW - Conformation

KW - Episodic memory

KW - Epitope

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=0036434880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036434880&partnerID=8YFLogxK

U2 - 10.1006/exnr.2002.8014

DO - 10.1006/exnr.2002.8014

M3 - Article

C2 - 12429193

AN - SCOPUS:0036434880

VL - 177

SP - 475

EP - 493

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 2

ER -