PMID- 16257094
OWN - NLM
STAT- MEDLINE
DCOM- 20061026
LR  - 20220331
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 27
IP  - 11
DP  - 2006 Nov
TI  - Genetic correlates of behavioral endophenotypes in Alzheimer disease: role of 
      COMT, 5-HTTLPR and APOE polymorphisms.
PG  - 1595-603
AB  - Several studies have been conducted to understand the genetic correlates of 
      Alzheimer disease (AD)-related behavioral and psychological symptoms in dementia 
      (BPSD). However, given that BPSD rarely occur in isolation, it has been suggested 
      that targeting BPSD individually is too narrow of an approach if one wants to 
      accurately define all the associated risk factors. To date, we know of no work on 
      genetic polymorphisms related to behavioral endophenotypes in AD. The present 
      study sought to evaluate the relationship between such behavioral endophenotypes 
      in AD and genetic variations in dopamine- or serotonin-related genes, such as 
      catechol-O-methyltransferase (COMT) or 5-HTT gene-linked promoter region 
      (5-HTTLPR), and apolipoprotein E (APOE). Among 232 AD patients who underwent 
      clinical and neuropsychological examination, a behavioral and psychiatric 
      evaluation, and genotyping at COMT, 5-HTTPLR, and APOE; 66.4% showed more than 
      one behavioral symptom. By Principal Component Analysis of Neuropsychiatric 
      Inventory (NPI) symptoms four endophenotypes were identified, these were termed 
      "psychosis", "moods", "apathy", and "frontal". Modeling NPI 
      symptom-endophenotype-genotype relationships, and taking into account possible 
      confounds (i.e. demographic characteristics, comorbidities, concomitant 
      pharmacological treatments, and disease severity) by latent variable models, COMT 
      and 5-HTTLPR genetic variations correlated with "frontal" and "psychosis" 
      endophenotypes. APOE genotype did not correlate with any endophenotype. These 
      findings suggest that the possibility of identifying distinct phenotypes on a 
      genetic basis among AD patients exists, and suggest that clustering of BPSD into 
      endophenotypes might provide a new strategy for guiding future research on this 
      issue.
FAU - Borroni, B
AU  - Borroni B
AD  - Center for Aging Brain and Dementia, Department of Neurology, University of 
      Brescia, Italy. bborroni@inwind.it
FAU - Grassi, M
AU  - Grassi M
FAU - Agosti, C
AU  - Agosti C
FAU - Costanzi, C
AU  - Costanzi C
FAU - Archetti, S
AU  - Archetti S
FAU - Franzoni, S
AU  - Franzoni S
FAU - Caltagirone, C
AU  - Caltagirone C
FAU - Di Luca, M
AU  - Di Luca M
FAU - Caimi, L
AU  - Caimi L
FAU - Padovani, A
AU  - Padovani A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051027
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Apolipoproteins E)
RN  - 0 (SLC6A4 protein, human)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/complications/*genetics/*psychology
MH  - Apolipoproteins E/*genetics
MH  - Catechol O-Methyltransferase/*genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Models, Biological
MH  - Polymorphism, Genetic
MH  - Serotonin Plasma Membrane Transport Proteins/*genetics
MH  - Severity of Illness Index
EDAT- 2005/11/01 09:00
MHDA- 2006/10/27 09:00
CRDT- 2005/11/01 09:00
PHST- 2004/11/21 00:00 [received]
PHST- 2005/08/02 00:00 [revised]
PHST- 2005/09/25 00:00 [accepted]
PHST- 2005/11/01 09:00 [pubmed]
PHST- 2006/10/27 09:00 [medline]
PHST- 2005/11/01 09:00 [entrez]
AID - S0197-4580(05)00301-5 [pii]
AID - 10.1016/j.neurobiolaging.2005.09.029 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2006 Nov;27(11):1595-603. doi: 
      10.1016/j.neurobiolaging.2005.09.029. Epub 2005 Oct 27.