Heredity in dementia of the Alzheimer type

Bergem, Astrid Liv Mina

doi:10.1111/j.1399-0004.1994.tb04216.x

Cited by 27 publications

(9 citation statements)

References 47 publications

(35 reference statements)

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“…Recurrence risk among siblings of those with AD (λ S ) have consistently ranged between four and five times higher than the risk to the general population (Hirst et al, 1994; Pericak-Vance et al, 1988; Sadovnick et al, 1989). Twin studies found higher concordance of AD among monozygotic twins (22-83%) than dizygotic twins (0-50%) (Bergem, 1994; Bergem et al, 1997; Breitner et al, 1993; Breitner et al, 1995), lending further support to genetic contributions to AD over only shared environmental contributors. Among early-onset families, patterns of AD inheritance have been consistent with classical Mendelian autosomal dominant inheritance, while the late-onset families have tended to suggest a multifactorial inheritance involving both genetic and non-genetic factors (Farrer et al, 1991; Rao et al, 1994; van Duijn et al, 1993).…”

Section: Alzheimer’s Disease: Characteristics Epidemiology and Genementioning

confidence: 91%

“…While APOE is a critical contributor to genetic risk, more than a third of AD cases do not carry any APOE ε4 alleles, and as AD heritability has been estimated at ~80% (Bergem, 1994), this suggests much of the heritability has not yet been characterized. At most, APOE may account for 50% of the total genetic effect in AD (Farrer et al, 1997; Roses et al, 1995; Saunders et al, 1993).…”

Section: Genetics Of Alzheimer Disease: Late-onset Alzheimer Disease mentioning

confidence: 99%

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Genomic variants, genes, and pathways of Alzheimer's disease: An overview

Naj

Schellenberg

2016

American J of Med Genetics Pt B

165

125

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Alzheimer’s disease (AD) (MIM: 104300) is a highly heritable disease with great complexity in its genetic contributors, and represents the most common form of dementia. With the gradual aging of the world’s population, leading to increased prevalence of AD, and the substantial cost of care for those afflicted, identifying the genetic causes of disease represents a critical effort in identifying therapeutic targets. Here we provide a comprehensive review of genomic studies of AD, from the earliest linkage studies identifying monogenic contributors to early-onset forms of AD to the genome-wide and rare variant association studies of recent years that are being used to characterize the mosaic of genetic contributors to late-onset AD (LOAD), and which have identified approximately ~20 genes with common variants contributing to LOAD risk. In addition, we explore studies employing alternative approaches to identify genetic contributors to AD, including studies of AD-related phenotypes and multi-variant association studies such as pathway analyses. Finally, we introduce studies of next-generation sequencing, which have recently helped identify multiple low-frequency and rare variant contributors to AD, and discuss on-going efforts with next-generation sequencing studies to develop statistically well-powered and comprehensive genomic studies of AD. Through this review, we help uncover the many insights the genetics of AD have provided into the pathways and pathophysiology of AD.

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Section: Alzheimer’s Disease: Characteristics Epidemiology and Genementioning

confidence: 91%

Section: Genetics Of Alzheimer Disease: Late-onset Alzheimer Disease mentioning

confidence: 99%

Genomic variants, genes, and pathways of Alzheimer's disease: An overview

Naj

Schellenberg

2016

American J of Med Genetics Pt B

165

125

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“…Since heredity is reported to be a major risk factor for the development of AD, whereas environmental factors dominate in VaD (Bergem 1994), we have compared APOE alleles in blood samples from Norwegian twin pairs suffering from AD and VaD. In this population-based sample of 72 twin pairs, there were 38 AD and 22 VaD pairs. Among the AD twin pairs the probandwise concordance (both twins affected) rate was 83.2% in monozygotic (MZ) and 46.6% in dizygotic (DZ) pairs respectively, an observation which indicates that AD is heavily genetically determined.…”

mentioning

confidence: 99%

Apolipoprotein E type ε4 allele, heritability and age at onset in twins with Alzheimer disease and vascular dementia

Bergem

Lannfelt²

1997

Clinical Genetics

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The apolipoprotein E (APOE) ε4 allele is a risk factor in Alzheimer disease (AD), but not in vascular dementia (VaD). We have investigated whether the ε4 allele is more common in twin pairs concordant for AD, compared with those discordant for AD, and whether the ε4 allele is more common in AD twins than in VaD twins. In addition, we have investigated the relationship of the ε4 allele and the age at onset in AD and VaD. APOE genotype was analysed in 29 senile demented twin pairs. The ε4 allele was associated with AD and not with VaD. However, there was no difference in the frequency of the APOE ε4 allele in concordant (33.3%) and discordant (31.3%) AD dizygotic twin pairs. Age at onset in AD was significantly lower in ε4 homozygotes than in individuals with one or no copies of ε4 (62.4 vs. 73.5, p < 0.01). In concordant AD twin pairs, the ε4 allele frequency was somewhat higher in the twins with earlier onset (41.7% vs. 25%), but the difference was not statistically significant. In the VaD group the age at onset was not significantly different between individuals with or without ε4 in their genotypes.

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“…The most studied trigger of AD is genetic background. According to estimations, based on human pedigree analysis, up to 80% of all Alzheimer's cases are hereditary (Bergem, 1994). The first genes that were identified as genes in which mutations lead to fAD were: APP, BACE, and gamma-secretase genes, called PSEN1 and PSEN2.…”

Section: Hereditary Variance Of Amyloid Ptmsmentioning

confidence: 99%