scholarly journals Evidence for Allelic Heterogeneity in Familial Early-Onset Alzheimer's Disease

1991 ◽  
Vol 158 (4) ◽  
pp. 471-474 ◽  
Author(s):  
Cornelia M. Van Duijn ◽  
Christine Van Broeckhoven ◽  
John A. Hardy ◽  
Alison M. Goate ◽  
Martin N. Rossor ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Epidemiological Study ◽  
Genetic Counselling ◽  
Early Onset ◽  
Age Of Onset ◽  
Population Based ◽  
Chromosome 21 ◽  
Allelic Heterogeneity ◽  
Early Onset Alzheimer’S Disease

Age of onset was examined for 139 members of 30 families affected by early-onset AD. Most (77%) of the variance of age of onset derived from differences between rather than within families. The constancy of age of onset within families was also observed in an analysis restricted to families derived from a population-based epidemiological study with complete ascertainment of early-onset AD. Furthermore, we observed clustering of age of onset within those families that support linkage to the predisposing locus on chromosome 21. Our data are compatible with the view that allelic heterogeneity at the AD locus may account for the similarity in age of onset within families. This finding may be of value for scientific studies of AD as well as for genetic counselling.

A Family with Multiple Instances of Definite, Probable and Possible Early-Onset Alzheimer's Disease

1991 ◽  
Vol 159 (4) ◽  
pp. 524-530 ◽  
Author(s):  
H. Karlinsky ◽  
E. Madrick ◽  
J. Ridgley ◽  
J. M. Berg ◽  
R. Becker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Age Of Onset ◽  
Diagnostic Difficulties ◽  
History Of ◽  
Early Onset Alzheimer’S Disease ◽  
The Mean ◽  
Age Of Death

A family with a multigenerational history of proven or suspected early-onset Alzheimer's disease (AD) consistent with autosomal-dominant inheritance is described. To date, the pedigree comprises five generations in which there are 13 known affected individuals. The mean age of onset of cognitive deficits in those for whom data are available (n = 11) is 47.6 (s.d. 3.0) years and the mean age of death (n = 10) is 58.8 (s.d. 4.0) years. The variability in the extent and quality of available data illustrates the diagnostic difficulties encountered in ascertaining such an extended pedigree, and the need for caution in interpreting the evidence.

Early onset Alzheimer’s disease

2020 ◽  
pp. 75-82
Author(s):  
Ratnavalli Ellajosyula
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Geographical Location ◽  
Epidemiological Studies ◽  
Incidence Rates ◽  
Prevalence Rates ◽  
Early Onset Alzheimer’S Disease

The term ‘early onset Alzheimer’s disease’ (EOAD) is used when symptoms of Alzheimer’s disease (AD) occur in patients younger than 65 years. EOAD is an uncommon condition and data on epidemiology is limited. Prevalence rates range from 15 to 200 and incidence rates 2.4–22.6 per 100,000 population. Prevalence rates increase with age similar to that for late onset AD. The prevalence of autosomal dominant EOAD is 5.2 per 100,000. Half of these patients have an underlying mutation in amyloid precursor protein, presenilin 1 or 2 genes. Apolipoprotein E genotype is a risk factor for EOAD and homozygotes have an earlier age of onset. Methodological issues and geographical location make comparisons across epidemiological studies difficult. Further cross-national and cross-cultural studies with standardized methodology are necessary to understand the role of risk and protective factors, as well as to estimate the burden of the disease.

scholarly journals Genetic association of the presenilin-1 regulatory region with early-onset Alzheimer's disease in a population-based sample

1999 ◽  
Vol 7 (7) ◽  
pp. 801-806 ◽  
Author(s):  
Cornelia M van Duijn ◽  
Marc Cruts ◽  
Jessie Theuns ◽  
Geert Van Gassen ◽  
Hubert Backhovens ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Association ◽  
Early Onset ◽  
Regulatory Region ◽  
Population Based ◽  
Presenilin 1 ◽  
Early Onset Alzheimer’S Disease

Progress in Molecular Genetics of Alzheimer's Disease

1996 ◽  
Vol 2 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Fuki M. Hisama ◽  
Gerard D. Schellenberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Positional Cloning ◽  
Age Of Onset ◽  
Late Onset ◽  
Chromosome 21 ◽  
Chromosome 1 ◽  
Amyloid Precursor Protein Gene ◽  
Chromosome 14

Recent intensive work has highlighted the genetic basis of several forms of Alzheimer's disease (AD). Mutations in the amyloid precursor protein gene on chromosome 21 can cause either an early-onset autosomal dominant AD or hereditary cerebral hemorrhage with amyloidosis. On chromosome 14, a second gene associated with 70 to 90% early-onset familial AD (FAD) was identified by positional cloning in 1995. Still other kindreds show no linkage to either chromosome 21 or chromosome 14; the third locus (on chromosome 1) was recently identified in affected descendants of a group of families known as the Volga Germans. In late-onset (age >65 years) AD, the apolipoprotein E gene allele ∊e4 on chromosome 19 has clearly been shown to be a risk factor for the development of AD and appears to modify the age of onset of the disease. The emerging picture is that AD is a genetically complex, heterogeneous disorder. Precisely how these genetic factors interact with each other and with other yet-to-be-identified genetic and nongenetic (environmental) factors to produce the clinical and pathologic findings in AD remains to be elucidated. The Neuroscientist 2:3–6, 1996

scholarly journals Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Justin L. Tosh ◽  
◽  
Elena R. Rhymes ◽  
Paige Mumford ◽  
Heather T. Whittaker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Precursor Protein ◽  
Mouse Models ◽  
Early Onset ◽  
Amyloid Β ◽  
Chromosome 21 ◽  
Extra Copy ◽  
Early Onset Alzheimer’S Disease

AbstractIndividuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.

scholarly journals Estrogen use and early onset Alzheimer's disease: a population-based study

1999 ◽  
Vol 67 (6) ◽  
pp. 779-781 ◽  
Author(s):  
A. J C Slooter ◽  
J. Bronzova ◽  
J. C M Witteman ◽  
C. Van Broeckhoven ◽  
A. Hofman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Population Based ◽  
Population Based Study ◽  
Early Onset Alzheimer’S Disease

Age of onset in familial early onset Alzheimer's disease correlates with genetic aetiology

1993 ◽  
Vol 48 (3) ◽  
pp. 129-130 ◽  
Author(s):  
Michael Mullan ◽  
Henry Houlden ◽  
Fiona Crawford ◽  
Angus Kennedy ◽  
Penelope Rogues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Age Of Onset ◽  
Early Onset Alzheimer’S Disease

scholarly journals Genetic dissection of Down syndrome-associated alterations in APP/amyloid-β biology using mouse models

2020 ◽  
Author(s):  
Justin L. Tosh ◽  
Ellie Rhymes ◽  
Paige Mumford ◽  
Heather T. Whittaker ◽  
Laura J. Pulford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Precursor Protein ◽  
Mouse Models ◽  
Early Onset ◽  
Amyloid Β ◽  
Chromosome 21 ◽  
Extra Copy ◽  
Early Onset Alzheimer’S Disease

AbstractIndividuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.

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