Genetics
CETP gene variants are associated with neuropsychiatric symptom severity in Alzheimer's disease (Braz J Psychiatry 2017)
Original title: Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer's disease dementia
In 201 consecutive outpatients with late-onset Alzheimer's disease, researchers examined associations between cerebrovascular metabolism genotypes and haplotypes, including CETP variants I422V and TaqIB, and age at dementia onset and neuropsychiatric symptoms. Only APOE-e4 carriage was linked to earlier dementia onset, along with less apathy, more delusions and more aberrant motor behaviour. CETP variants carrying the G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviours, while severely impaired carriers of the T allele of the NR1H2 variant rs2695121 had more anxiety and more aberrant motor behaviour. The authors conclude that while only APOE haplotypes affected age at onset, cerebrovascular metabolism genotypes including CETP were associated with differences in several neuropsychiatric manifestations of Alzheimer's disease.
Original abstract
Objective:: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer's disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage.
Methods:: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121.
Results:: Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior.
Conclusion:: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.