Familial influence on variation in age of onset and behavioural phenotype in Alzheimer's disease.
BACKGROUND
Alzheimer's disease manifests considerable heterogeneity, the cause of which is unknown.


OBJECTIVE
To determine the familial (genotypic) influence on phenomenology (phenotype) in Alzheimer's disease.


METHODS
Affected sibling pairs with Alzheimer's disease were assessed for a range of cognitive and non-cognitive symptoms. Resemblance for phenotypic characteristics was estimated using intraclass correlations for continuous traits and by pairwise concordance for dichotomous traits. The relationship between age of onset and APOE genotype was examined using linear regression analysis.


RESULTS
Significant familial effects on age of onset (intraclass correlation 0.41) and mood state (intraclass correlation 0.26), and a relatively high pairwise concordance for agitation (excess concordance 0.1) were found. The APOE locus was found to account for 4% of the variance in age of onset.


CONCLUSIONS
Substantial familial influence on age of onset, depression and agitation suggests that genotype does influence phenotype in Alzheimer's disease. Establishing the molecular basis for this phenotypic variation may prove relevant to other neuropsychiatric disorders.
Tunstall
N
N
Department of Psychiatry, Institute of Psychiatry, London.
Owen
M J
MJ
Williams
J
J
Rice
F
F
Carty
S
S
Lillystone
S
S
Fraser
L
L
Kehoe
P
P
Neill
D
D
Rudrasingham
V
V
Sham
P
P
Lovestone
S
S
D000339:Affect; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D003321:Cornell Medical Index; D005260:Female; D005824:Genetics, Behavioral; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype