Deposition of Hyperphosphorylated Tau in Cerebellum of PS1 E280A Alzheimer's Disease

被引：71

作者：

Sepulveda-Falla, Diego ^{[1
,2
]}

Matschke, Jakob ^{[1
]}

Bernreuther, Christian ^{[1
]}

Hagel, Christian ^{[1
]}

Puig, Berta ^{[1
]}

Villegas, Andres ^{[2
]}

Garcia, Gloria ^{[2
]}

Zea, Julian ^{[2
]}

Gomez-Mancilla, Baltazar ^{[3
]}

Ferrer, Isidre ^{[4
]}

Lopera, Francisco ^{[2
]}

Glatzel, Markus ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, D-20246 Hamburg, Germany

[2] Univ Antioquia, Fac Med, Neurosci Grp Antioquia, Medellin, Colombia

[3] Novartis Pharma AG, Inst BioMed Res, Neurosci Discovery, Basel, Switzerland

[4] Univ Barcelona, IDIBELL Univ Hosp Bellvitge, CIBERNED, Pathol Anat Serv,Inst Neuropathol, Lhospitalet De Llobregat, Spain

来源：

BRAIN PATHOLOGY | 2011年 / 21卷 / 04期

关键词：

cerebellum; familial Alzheimer's disease; neuropathology; presenilin-1; Tau protein; EXTRACELLULAR NEUROFIBRILLARY TANGLES; CEREBRAL AMYLOID ANGIOPATHY; PRESENILIN-1; MUTATION; PRION PROTEIN; NEURONAL LOSS; ONSET; PLAQUES; PHENOTYPE; CORTEX; BRAIN;

D O I：

10.1111/j.1750-3639.2010.00469.x

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Early-onset familial Alzheimer's disease (AD) caused by presenilin-1 mutation E280A (PS1-E280A) presents wide clinical and neuropathological variabilities. We characterized clinically and neuropathologically PS1-E280A focusing in cerebellar involvement and compared it with early-onset sporadic Alzheimer's disease (EOSAD). Twelve E280A brains and 12 matched EOSAD brains were analyzed for beta-amyloid and hyperphosphorylated tau (pTau) morphology, beta-amyloid subspecies 1-40, 1-42 levels, pTau levels, and expression of stress kinases in frontal cortex and cerebellum. The data were correlated to clinical and genetic findings. We observed higher beta-amyloid load, beta-amyloid 1-42 and pTau concentrations in frontal cortex of PS1-E280A compared with EOSAD. High beta-amyloid load was found in the cerebellum of PS1-E280A and EOSAD patients. In PS1-E280A, beta-amyloid localized to the molecular and Purkinje cell layers, whereas EOSAD showed them in Purkinje and granular cell layers. Surprisingly, 11 out of 12 PS1-E280A patients showed deposition of pTau in the cerebellum. Also, seven out of 12 PS1-E280A patients presented cerebellar ataxia. We conclude that deposition of beta-amyloid in the cerebellum is prominent in early-onset AD irrespective of genetic or sporadic origin. The presence of pTau in cerebellum in PS1-E280A underscores the relevance of cerebellar involvement in AD and might be correlated to clinical phenotype.

引用

页码：452 / 463

页数：12

共 48 条

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