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GENATLAS PHENOTYPE
last update : 13-06-2017
Symbol AD3
Location 14q24.2
HGNC id 183
Name Alzheimer disease 3
Other name(s) Alzheimer disease 3, early onset familial
Corresponding gene PSEN1
Other symbol(s) FAD, EOFAD, ADEOAD
Main clinical features
  • adult onset progressive dementia before age 60 to 65 years
  • cerebral cortical atrophy by neuroimaging studies
  • beta-amyloid neuritic plaques and intraneuronal neurofibrillary tangles at postmortem examination
    • Genetic determination autosomal dominant
    Function/system disorder psychiatric disorder
    Type disease
    Gene product
    Name presenilin 1
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/gain of function ~40 mutations described. dominant mutations leading to defective processing of APP beta with an increase of the extracellular concentration of amyloid precursor protein longer isoform A beta 42
    abnormal splicing     1/40 mutations with loss of exon 9
    Remark(s) - three forms of early onset familial AD caused by mutations in one of three genes APP(10-15 percent), PSEN1 (30-70 percent) and PSEN2 (<5 percent of patients) are recognised ; - mutations linked to familial Alzheimer disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism
  • exhibited numerous ring-like NF-positive and elongated tau-labelled dystrophic neurites, whereas these dystrophic neurite types were only abundant at the very early (pathologically aged cases) or very late stages of sporadic AD progression, respectively (Woodhouse 2009)