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

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, betaamyloid 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.

• Autores: Sepúlveda Falla, Diego Alonso; Villegas Lanau, Carlos Andrés; García Ospina, Gloria Patricia; Zea Lopera, Julián; Lopera Restrepo, Francisco Javier
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2011
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/32145
• Acceso en línea: https://hdl.handle.net/10495/32145
• Palabra clave: Enfermedad de Alzheimer; Alzheimer Disease; Cerebelo; Cerebellum; Neuropatología; Neuropathology; Presenilina-1; Presenilin-1; Proteínas tau; tau Proteins; Péptidos beta-Amiloides; Amyloid beta-Peptides
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/