<var date-time="VBbz4A"></var> Skip to main page content (VSports)
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or VSports app下载. mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

Meta-Analysis
. 2014 Jul 15;83(3):253-60.
doi: 10.1212/WNL.0000000000000596. Epub 2014 Jun 13.

"V体育安卓版" Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis

Davis C Ryman  1 , Natalia Acosta-Baena  2 , Paul S Aisen  2 , Thomas Bird  2 , Adrian Danek  2 , Nick C Fox  2 , Alison Goate  2 , Peter Frommelt  2 , Bernardino Ghetti  2 , Jessica B S Langbaum  2 , Francisco Lopera  2 , Ralph Martins  2 , Colin L Masters  2 , Richard P Mayeux  2 , Eric McDade  2 , Sonia Moreno  2 , Eric M Reiman  2 , John M Ringman  2 , Steve Salloway  2 , Peter R Schofield  2 , Reisa Sperling  2 , Pierre N Tariot  2 , Chengjie Xiong  2 , John C Morris  2 , Randall J Bateman  2 ; Dominantly Inherited Alzheimer Network
Affiliations
Meta-Analysis

Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis (VSports在线直播)

Davis C Ryman et al. Neurology. .

VSports最新版本 - Abstract

Objective: To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD VSports手机版. .

Methods: We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study V体育安卓版. .

Results: We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10(-16), r2 > 0. 38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex. V体育ios版.

Conclusions: Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research VSports最新版本. .

PubMed Disclaimer

Figures

Figure 1
Figure 1. Age at symptom onset by mutated gene
Age at symptom onset for all affected individuals are shown grouped by the gene affected by their autosomal dominant Alzheimer disease mutation, with APP mutations having an additional subclass for gene duplications. APP = amyloid precursor protein; PS1 = presenilin 1; PS2 = presenilin 2.
Figure 2
Figure 2. Individual age at symptom onset vs measures of family onset history
The actual age at symptom onset for each affected individual is shown on the y-axis, plotted against values predicted from family history on the x-axis. (A) Each individual's age at onset vs the reported age at onset of their affected parent. (B) Each individual's age at onset vs the mean age at onset for all other individuals in their extended family. (C) Each individual's age at onset vs the mean age at onset for all other individuals sharing the same autosomal dominant Alzheimer disease mutation type. Plot points for each individual are colored according to their study of origin, as shown in the legend at the upper right. Jitter was added to the x- and y-axes for easier visualization. Regression lines and adjusted r2 values showing correlations between individual age at onset and each of these family history measures are displayed on the respective figures. DIAN = Dominantly Inherited Alzheimer Network.
Figure 3
Figure 3. Age at onset differences by APOE genotype
For affected individuals with known APOE genotype, the difference between each individual's actual age at onset and the mean age at onset of all others sharing the same autosomal dominant Alzheimer disease mutation type is plotted on the y-axis.
Figure 4
Figure 4. Age at symptom onset vs disease course in years
(A) For all individuals with known ages of symptom onset and death, age at symptom onset is plotted against disease course in years, estimated as the total time from symptom onset to death. Jitter was added to the x- and y-axes. A nonparametric smoothing function (LOESS) is shown in blue. Dashed red lines indicate median age at symptom onset and median survival from symptom onset in sporadic Alzheimer disease based on published data. (B) Individuals are shown partitioned into 3 groups by age at symptom onset.
See this image and copyright information in PMC

References

    1. Müller U, Winter P, Graeber MB. A presenilin 1 mutation in the first case of Alzheimer's disease. Lancet Neurol 2013;12:129–130 - PubMed
    1. Bateman RJ, Aisen PS, De Strooper B, et al. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimers Res Ther 2011;3:1. - PMC - PubMed
    1. Mann DM, Pickering-Brown SM, Takeuchi A, Iwatsubo T. Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease. Am J Pathol 2001;158:2165–2175 - PMC (V体育2025版) - PubMed
    1. Larner AJ, Doran M. Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene. J Neurol 2006;253:139–158 - PubMed
    1. Wijsman EM, Daw EW, Yu X, et al. APOE and other loci affect age-at-onset in Alzheimer's disease families with PS2 mutation. Am J Med Genet B Neuropsychiatr Genet 2005;132B:14–20 - PubMed (V体育官网)

"V体育安卓版" Publication types