Genetic correlates of behavioral endophenotypes in Alzheimer disease: Role of COMT, 5-HTTLPR and APOE polymorphisms

Borroni, Barbara; Grassi, Mario; Agosti, Chiara; Costanzi, Chiara; Archetti, Silvana; Franzoni, Simone; Caltagirone, Carlo; Luca, Monica Di; Caimi, Luigi; Padovani, Alessandro

doi:10.1016/j.neurobiolaging.2005.09.029

Cited by 74 publications

(61 citation statements)

References 41 publications

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“…The high prevalence of heterozygous and homozygous APOE 4 carriers enabled an analysis of the APOE 4 dose. The fact that earlier studies assessing neuropsychiatric and behavioral symptoms in relation to APOE status often analyzed the dichotomized APOE 4 status rather than the number of APOE 4 alleles may partially account for their negative findings [ [15][16][17][18] . Remarkably, a recent study that found no association between APOE 4 genotype and neuropsychiatric and behavioral symptoms in AD did report an association between APOE 4 and aggression in patients with frontotemporal lobar degeneration, and with delusions in patients with dementia with Lewy bodies [26] .…”

Section: Discussionmentioning

confidence: 99%

“…However, results of former studies assess- 43 ing neuropsychiatric and behavioral phenotype in relation to APOE genotype have been inconsistent. Some studies have been negative [15][16][17][18] , whereas positive associations -especially with psychotic symptoms and aggressive behavior -have been found by others [19][20][21][22] . The former inconsistent findings may be due to methodological issues.…”

Section: Introductionmentioning

confidence: 99%

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Apolipoprotein E Genotype Influences Presence and Severity of Delusions and Aggressive Behavior in Alzheimer Disease

Flier¹,

Staekenborg²,

Pijnenburg³

et al. 2006

Dement Geriatr Cogn Disord

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Aim: We investigated differences in the prevalence and severity of 10 neuropsychiatric and behavioral symptoms according to apolipoprotein E (APOE) genotype and dementia severity in Alzheimer disease (AD). Methods: Neuropsychiatric and behavioral symptoms of 110 AD patients were assessed using the Neuropsychatric Inventory. Dementia severity was assessed using the Mini Mental State Examination (MMSE). Results: There were 27 APOE-Ε4-negative patients, 65 heterozygous patients and 18 homozygous patients. There was a significant association between the number of APOE Ε4 alleles and prevalence and severity of neuropsychiatric and behavioral symptoms that was mainly attributable to delusions and agitation/aggression, which were more common and severer among homozygous APOE Ε4 carriers. In addition, the presence of hallucinations, anxiety, apathy and aberrant motor behavior increased with deteriorating MMSE score, independently of APOE Ε4 status. Conclusions: The present study showed that the APOE Ε4 genotype modifies neuropsychiatric and behavioral phenotype in AD. In particular, it was shown that delusions and agitation/aggression were more common and severer among homozygous APOE Ε4 carriers than among heterozygous or APOE-Ε4-negative patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E Genotype Influences Presence and Severity of Delusions and Aggressive Behavior in Alzheimer Disease

Flier¹,

Staekenborg²,

Pijnenburg³

et al. 2006

Dement Geriatr Cogn Disord

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show abstract

“…The serotonin transporter promoter region (5HT-TPR) also has been implicated in AD+D. Homozygosity for the long arm leads to an increase in 5HTT mRNA transcription and 5HT uptake compared with genes containing at least one short arm and is protective for AD+D [46]. The dopaminergic system also has been investigated, with dopamine receptor DRD3 1/1 allele implicated in delusions compared with the DRD3 2/2 allele [47].…”

Section: Geneticsmentioning

confidence: 99%

Neurobiology of Delusions in Alzheimer’s Disease

Ismail

Nguyen

Fischer

et al. 2011

Curr Psychiatry Rep

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Alzheimer's disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles of serotonergic, muscarinic, nicotinic, or Apoε4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities.Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between these two syndromes is essential to making progress in the area of delusions in AD.

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“…It is well established that AD is a heterogeneous disease characterized by a variety of BPSD beyond the well-known progressive cognitive decline [6,7,36]. Different clinical phenotypes might be influenced by underlying genetic variability and behavioral and psychological symptoms.…”

Section: Discussionmentioning

confidence: 99%

Catechol-O-Methyltransferase GeneticVariant Associated with the Risk of Alzheimers Disease in a Brazilian Population

Pereira

Romano-Silva

Bicalho

et al. 2012

Dement Geriatr Cogn Disord

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The aim of the present study was to examinethe association between polymorphism in thecatechol-O-methyltransferase(COMT) gene and Alzheimer’s disease (AD) in a Brazilianpopulation. The case-control method was used to study the association between AD and geneticvariants of COMT. Six tag single-nucleotide polymorphisms(SNPs) in the COMT gene were genotyped by RT-PCR. Ourfindings showed that the 6 tag SNPs analyzed in this study were not associated with AD at the alleleand genotype levels in comparison with the control group. No statistical difference was foundbetween groups with and without behavioral and psychological symptoms of dementia (BPSD). Ourresults do not support the hypothesis that the polymorphisms of theCOMT gene may be associated with susceptibility to AD withand without BPSD.

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Genetic correlates of behavioral endophenotypes in Alzheimer disease: Role of COMT, 5-HTTLPR and APOE polymorphisms

Cited by 74 publications

References 41 publications

Apolipoprotein E Genotype Influences Presence and Severity of Delusions and Aggressive Behavior in Alzheimer Disease

Apolipoprotein E Genotype Influences Presence and Severity of Delusions and Aggressive Behavior in Alzheimer Disease

Neurobiology of Delusions in Alzheimer’s Disease

Catechol-O-Methyltransferase GeneticVariant Associated with the Risk of Alzheimers Disease in a Brazilian Population

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Genetic correlates of behavioral endophenotypes in Alzheimer disease: Role of COMT, 5-HTTLPR and APOE polymorphisms

Cited by 74 publications

References 41 publications

Apolipoprotein E Genotype Influences Presence and Severity of Delusions and Aggressive Behavior in Alzheimer Disease

Apolipoprotein E Genotype Influences Presence and Severity of Delusions and Aggressive Behavior in Alzheimer Disease

Neurobiology of Delusions in Alzheimer’s Disease

Catechol-O-Methyltransferase GeneticVariant Associated with the Risk of Alzheimers Disease in a Brazilian Population

Contact Info

Product

Resources

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Catechol-O-Methyltransferase GeneticVariant Associated with the Risk of Alzheimers Disease in a Brazilian Population