The effects of APOE and tau gene variability on risk of frontotemporal dementia

Bernardi, Livia; Maletta, Raffaele; Tomaino, Carmine; Smirne, Nicoletta; Natale, Michele Di; Perri, Maria; Longo, Teresa; Colao, Rosanna; Curcio, Sabrina A.M.; Puccio, Gianfranco; Mirabelli, Maria; Kawarai, Toshitaka; Rogaeva, Ekaterina; George-Hyslop, Peter St; Passarino, Giuseppe; Benedictis, G. De; Bruni, Amalia C.

doi:10.1016/j.neurobiolaging.2005.03.008

Cited by 55 publications

(47 citation statements)

References 50 publications

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“…This association was even stronger in APOE 4 negatives. 11,12,14 In our study including IBMPFD subjects we found no association between MAPT H2 haplotype and an increase risk of developing dementia.…”

Section: Discussioncontrasting

confidence: 73%

“…21,22 FTD is heterogeneous both clinically and pathologically. 23 An association between the fluent aphasic clinical form of FTD (but not other clinical FTD forms) and APOE 4 was found by Short et al 24 Recently, the APOE 4 allele has been found to be overrepresented in clinical FTD within a homogenous population in southern Italy, 14 and in neuropathologically-verified Pick's disease and dementia lacking distinctive histopathology (DLDH). 25 Tau pathology is characteristic of frontotemporal dementia associated with mutations in the MAPT gene on chromosome 17, and in a considerable proportion (40% in one series) of sporadic cases.…”

Section: Discussionmentioning

confidence: 98%

“…[7][8][9][10] Microtubule associated protein tau (MAPT) haplotype was also investigated because of its described modifier effect in frontotemporal lobar degeneration, and possibly in AD. [11][12][13][14] …”

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confidence: 99%

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APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD)

Mehta

Watts

Adamson

et al. 2007

Genetics in Medicine

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Purpose: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. Methods: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. Results and Conclusion: FTD was associated with APOE 4 genotype (P ϭ 0.0002), myopathy (P ϭ 0.0006), and age (P ϭ 0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P ϭ 0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype. Genet Med 2007:9(1):9-13.

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Section: Discussioncontrasting

confidence: 73%

Section: Discussionmentioning

confidence: 98%

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APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD)

Mehta

Watts

Adamson

et al. 2007

Genetics in Medicine

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“…[30][31][32] Furthermore, inconclusive results on APOE as a modifying factor for FTLD have been reported. 17,18,[33][34][35][36] It has also been speculated that rs5848 in the 3 0 UTR of GRN is a binding site for the micro-RNA miR-659 and may regulate the translation of the GRN mRNA. 37,38 Investigating these three modifying genes in our patient cohort did not reveal any association with age at onset or GRN levels in GRN-mutation carriers or the complete cohort.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration

et al. 2013

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“…Studies on the effect of apoE4 on FTLD have yielded contradictory results (15)(16)(17)(18), which likely reflects the complex clinical, pathological, and genetic underpinnings of this disease. The only prospective study that has investigated the effect of apoE genotype on clinical expression in frontotemporal dementia (FTD) revealed an 4 dose-dependent influence on behavioral symptoms in behavioral variant frontotemporal dementia (bvFTD) (18).…”

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confidence: 99%

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

Agosta

Vossel

Miller

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

165

154

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Apolipoprotein 4 (apoE4) has been strongly linked with Alzheimer's disease (AD) and contributes to several other neurological disorders. We investigated the influence of 4 allele carrier status on the pattern of gray matter atrophy and disease severity in 51 patients with probable AD and 31 patients with behavioral variant frontotemporal dementia (bvFTD), compared with 56 healthy controls. Voxel-based morphometry was performed by using statistical parametric mapping. The 4 allele frequency was higher in the AD group (P < 0.001) than the controls but not in the bvFTD group. No differences in demographic or cognitive profiles were observed between 4 allele carriers and noncarriers within any of the diagnostic groups. However, 4 carrier status was associated with more severe brain atrophy in disease-specific regions compared with noncarriers in both AD and bvFTD. AD 4 carriers showed greater atrophy in the bilateral parietal cortex and right hippocampus, and bvFTD 4 carriers demonstrated greater atrophy in the bilateral medial, dorsolateral, and orbital frontal cortex, anterior insula, and cingulate cortex with right predominance. This regional 4 effect is consistent with the hypothesis that apoE may affect the morphologic expression uniquely in different neurodegenerative diseases. The atrophy patterns in 4 carriers may indicate that they are at greater risk for clinical progression.AD/FTD ͉ apoE ͉ brain morphometry

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The effects of APOE and tau gene variability on risk of frontotemporal dementia

Cited by 55 publications

References 50 publications

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD)

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD)

Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

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