Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer's disease.
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Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer's disease. / Sepulveda-Falla, Diego; Matschke, Jakob; Bernreuther, Christian; Hagel, Christian; Puig Martorell, Berta; Villegas, Andres; Garcia, Gloria; Zea, Julian; Gomez-Mancilla, Baltazar; Ferrer, Isidre; Lopera, Francisco; Glatzel, Markus.
In: BRAIN PATHOL, Vol. 21, No. 4, 4, 2011, p. 452-463.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer's disease.
AU - Sepulveda-Falla, Diego
AU - Matschke, Jakob
AU - Bernreuther, Christian
AU - Hagel, Christian
AU - Puig Martorell, Berta
AU - Villegas, Andres
AU - Garcia, Gloria
AU - Zea, Julian
AU - Gomez-Mancilla, Baltazar
AU - Ferrer, Isidre
AU - Lopera, Francisco
AU - Glatzel, Markus
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
M3 - SCORING: Journal article
VL - 21
SP - 452
EP - 463
JO - BRAIN PATHOL
JF - BRAIN PATHOL
SN - 1015-6305
IS - 4
M1 - 4
ER -
