The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimer's disease.
OBJECTIVE
Mutations in the amyloid precursor protein gene were the first to be recognized as a cause of Alzheimer's disease (AD).


METHODS
We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation.


RESULTS
In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far. Two subjects of the other family with AD diagnosis were carriers of the same mutation.


CONCLUSIONS
All AD subjects showed a cognitive profile characterized by early impairment in long-term memory, shifting abilities and affective symptoms beginning in the fifth decade of life.
Talarico
G
G
Department of Neurological Science, Memory Clinic, University Sapienza, Rome, Italy. giuseppina.talarico@uniroma1.it
Piscopo
P
P
Gasparini
M
M
Salati
E
E
Pignatelli
M
M
Pietracupa
S
S
Malvezzi-Campeggi
L
L
Crestini
A
A
Boschi
S
S
Lenzi
G L
GL
Confaloni
A
A
Bruno
G
G
D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D042241:Early Diagnosis; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree
D016564:Amyloid beta-Protein Precursor