About this item:

351 Views | 187 Downloads

Author Notes:

Agustín Ruiz, Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona 08029, Catalonia, Spain. Tel.: +34 934447318, Email: aruiz@fundacioace.com.

We would like to thank patients and controls who participated in this project.

We are indebted to Trinitat Port-Carbó and her family who are supporting Fundació ACE research programs.


Research Funding:

This work has been partially funded by the Ministerio de Educación y Ciencia (PCT-010000-2007-18), (DEX-580000-2008-4), (Gobierno de España), Corporación Tecnológica de Andalucía (08/211) and Agencia IDEA (841318)(Consejería de Innovación, Junta de Andalucía).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Geriatrics & Gerontology
  • Neurosciences
  • Neurosciences & Neurology
  • GWAS
  • Alzheimer's disease
  • SNP
  • Disease progression
  • Mixed models
  • Genetics
  • Pharmacogenetics
  • CD2AP
  • EPHA1

Exploratory analysis of seven Alzheimer's disease genes: disease progression

Show all authors Show less authors

Journal Title:

Neurobiology of Aging


Volume 34, Number 4


, Pages 1310.e1-1310.e7

Type of Work:

Article | Post-print: After Peer Review


The relationships between genome wide association study-identified and replicated genetic variants associated with Alzheimer's disease (AD) risk and disease progression or therapeutic responses in AD patients are almost unexplored. Seven hundred and one AD patients with at least 3 different cognitive evaluations and genotypic information for APOE and 6 genome wide association study-significant single-nucleotide polymorphisms were selected for this study. Mean differences in Global Deterioration Score and Mini Mental State Examination (MMSE) were evaluated using nonparametric tests, general linear model and mixed models for repeated measurements. Each chart was also reviewed for evidence of treatment with any cholinesterase inhibitor, memantine, or both. Relationships between therapeutic protocols, genetic markers, and progression were explored using stratified analysis looking for specific effects on progression in each therapeutic category separately. Neither calculation rendered a Bonferroni-corrected statistically significant difference in any genetic marker. Mixed model results suggested differences in the average point in MMSE test for patients carrying PICALM GA or AA genotype compared with GG carriers at the end of the follow-up (MMSE mean difference = -0.57; 95% confidence interval, -1.145 to 0.009; p = 0.047). This observation remained unaltered after covariate adjustments although it did not achieve predefined multiple testing significance threshold. The PICALM single-nucleotide polymorphism also displayed a significant effect protecting against rapid progression during pharmacogenetic assays although its observed effect displayed heterogeneity among AD therapeutic protocols (p = 0.039). None of the studied genetic markers were convincingly linked to AD progression or drug response. However, by using different statistical approaches, the PICALM rs3851179 marker displayed consistent but weak effects on disease progression phenotypes.

Copyright information:

© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote