Cortical pyroglutamate amyloid-β levels and cognitive decline in Alzheimer's disease.

Abstract:

:Posterior cingulate cortex (PCC) accumulates amyloid-β (Aβ) early in Alzheimer's disease (AD). The relative concentrations of full-length Aβ and truncated, pyroglutamate-modified Aβ (NpE3) forms, and their correlations to cognitive dysfunction in AD, are unknown. We quantified AβNpE3-42, AβNpE3-40, Aβ1-42, and Aβ1-40 concentrations in soluble (nonfibrillar) and insoluble (fibrillar) pools in PCC from subjects with an antemortem clinical diagnosis of no cognitive impairment, mild cognitive impairment, or mild-moderate AD. In clinical AD, increased PCC concentrations of Aβ were observed for all Aβ forms in the insoluble pool but only for Aβ1-42 in the soluble pool. Lower Mini-Mental State Exam and episodic memory scores correlated most strongly with higher concentrations of soluble and insoluble Aβ1-42. Greater neuropathology severity by Consortium to Establish a Registry for Alzheimer's Disease and National Institute on Aging-Reagan pathologic criteria was associated with higher concentrations of all measured Aβ forms, except soluble AβNpE3-40. Low concentrations of soluble pyroglutamate Aβ across clinical groups likely reflect its rapid sequestration into plaques, thus, the conversion to fibrillar Aβ may be a therapeutic target.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Pivtoraiko VN,Abrahamson EE,Leurgans SE,DeKosky ST,Mufson EJ,Ikonomovic MD

doi

10.1016/j.neurobiolaging.2014.06.021

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

12-9

issue

1

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(14)00454-0

journal_volume

36

pub_type

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