We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Deposition of Hyperphosphorylated Tau in Cerebellum of PS1 E280A Alzheimer's Disease.
- Authors
Sepulveda-Falla, Diego; Matschke, Jakob; Bernreuther, Christian; Hagel, Christian; Puig, Berta; Villegas, Andres; Garcia, Gloria; Zea, Julian; Gomez-Mancilla, Baltazar; Ferrer, Isidre; Lopera, Francisco; Glatzel, Markus
- Abstract
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.
- Subjects
ALZHEIMER'S disease; PHOSPHORYLATION; PRESENILINS; CEREBRAL cortex; PURKINJE cells; CEREBRAL amyloid angiopathy
- Publication
Brain Pathology, 2011, Vol 21, Issue 4, p452
- ISSN
1015-6305
- Publication type
Article
- DOI
10.1111/j.1750-3639.2010.00469.x