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Pyroglutamylated amyloid-β is associated with hyperphosphorylated tau and severity of Alzheimer's disease.

Abstract：

:Pyroglutamylated amyloid-β (pE(3)-Aβ) has been suggested to play a major role in Alzheimer's disease (AD) pathogenesis as amyloid-β (Aβ) oligomers containing pE(3)-Aβ might initiate tau-dependent cytotoxicity. We aimed to further elucidate the associations among pE(3)-Aβ, full-length Aβ and hyperphosphorylated tau (HP-τ) in human brain tissue. We examined 41 post mortem brains of both AD (n = 18) and controls. Sections from frontal and entorhinal cortices were stained with pE(3)-Aβ, HP-τ and full-length Aβ antibodies. The respective loads were assessed using image analysis and western blot analysis was performed in a subset of cases. All loads were significantly higher in AD, but when using Aβ loads as independent variables only frontal pE(3)-Aβ load predicted AD. In frontal and entorhinal cortices pE(3)-Aβ load independently predicted HP-τ load while non-pE(3)-Aβ failed to do so. All loads correlated with the severity of AD neuropathology. However, partial correlation analysis revealed respective correlations in the frontal cortex only for pE(3)-Aβ load only while in the entorhinal cortex respective correlations were seen for both HP-τ and non-pE(3)-Aβ loads. Mini Mental State Examination scores were independently predicted by entorhinal HP-τ load and by frontal pE(3)-Aβ load. Here, we report an association between pE(3)-Aβ and HP-τ in human brain tissue and an influence of frontal pE(3)-Aβ on both the severity of AD neuropathology and clinical dementia. Our findings further support the notion that pE(3)-Aβ may represent an important link between Aβ and HP-τ, and investigations into its role as diagnostic and therapeutic target in AD are warranted.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Mandler M,Walker L,Santic R,Hanson P,Upadhaya AR,Colloby SJ,Morris CM,Thal DR,Thomas AJ,Schneeberger A,Attems J

doi

10.1007/s00401-014-1296-9

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

67-79

issue

1

eissn

0001-6322

issn

1432-0533

journal_volume

128

pub_type

杂志文章

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