Hemorrhage is uncommon in new Alzheimer family with Flemish amyloid precursor protein mutation.
BACKGROUND
Most mutations in the amyloid precursor protein (APP) gene have been associated with familial Alzheimer disease (AD); however, some mutations within the Abeta-coding sequence have been described in families with recurrent cerebral hemorrhage. The APPAla692Gly (Flemish) mutation was reported in a family in which affected members developed hemorrhagic stroke, progressive dementia, or both.


OBJECTIVE
To describe clinical, neuropathologic, and genetic features of a family of British origin with the Flemish APP mutation.


METHODS
Clinical features of the proband and two affected relatives were obtained by history, examination, and medical record review. Some information on deceased affected relatives was obtained by informant interview. Neuropathologic examination was carried out on one case. DNA studies were carried out on three affected and three unaffected individuals.


RESULTS
Presenile dementia was present in a pattern consistent with dominant inheritance, with the APP692 mutation being found in all affecteds and no unaffecteds. The proband also had a cerebral hemorrhage, but was the only one of five affecteds to have this complication. Neuropathologic examination confirmed AD, congophilic angiopathy, and hemorrhagic infarction.


CONCLUSIONS
This expands the number of families reported with mutations in the coding region of the amyloid precursor protein gene. Cerebral hemorrhage appears to be less frequent in this family than in the previously reported Flemish pedigree with the same mutation.
Brooks
W S
WS
Prince of Wales Medical Research Institute, University of New South Wales, Barker Street, Randwick, Sydney, NSW 2031, Australia. w.brooks@unsw.edu.au
Kwok
J B J
JB
Halliday
G M
GM
Godbolt
A K
AK
Rossor
M N
MN
Creasey
H
H
Jones
A O
AO
Schofield
P R
PR
D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D014057:Tomography, X-Ray Computed; D044465:White People / Q000235:genetics
D016564:Amyloid beta-Protein Precursor