Early-onset familial Alzheimer's disease (EOFAD).
Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.
McGill Centre for Studies in Aging, McGill University Department of Neurology, Canada.
Liyong
L
Wu
Pedro
P
Rosa-Neto
Ging-Yuek R
GY
Hsiung
A Dessa
AD
Sadovnick
Mario
M
Masellis
Sandra E
SE
Black
Jianping
J
Jia
Serge
S
Gauthier
D017668:Age of Onset; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D003937:Diagnosis, Differential; D005817:Genetic Counseling; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2