| Symbol
| AD1
|
| Location
| 21q21.3
|
| Name
|
Alzheimer disease 1, early onset familial |
| Corresponding gene
|
APP
|
| Other symbol(s)
| ALZ, 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 |
|
| autosomal recessive |
| Related entries
| AD3, AD4
|
| Function/system disorder
| psychiatric disorder |
| Type
| disease
|
| Name
| amyloid beta A4 protein
|
| Gene mutation | Chromosome rearrangement | Effect | Comments |
|
|---|
| various types
|
|
| principally located at or near either the beta or gamma secretases cleavage sites, increasing the extracellular concentration of beta 42 (43), and including mutation APP692
| |
| duplication
|
| the duplication size may vary from 0.58-6.7Mb with a minimum crical interval including the APP gene
| |
| 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 ; APP locus duplication was observed in ~8p.cent of cases in a cohort of dominant early-onset AD patients |
| Genotype/Phenotype correlations
|
the three subtypes of EOFAD are clinically indistinguishable; duplication of APP locus is associated with cerebral amyloid angiopathy, intracerebral haemorrage and seizures
mutation (A673V) causes disease only in the homozygous state; the mutation consists of a C-to-T transition that results in an alanine-to-valine substitution at position 673 and is associated with early-onset dementia and multiple-domain mild cognitive impairment (PMID: 19286555)) |