Premium
F1–01–03: Gene‐wide and pathway analyses identify new susceptibility genes and pathways related to Alzheimer's disease
Author(s) -
Moskvina Valentina
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.04.042
Subject(s) - genome wide association study , biology , genetics , gene , genetic association , locus (genetics) , single nucleotide polymorphism , missing heritability problem , heritability , biological pathway , computational biology , genotype , gene expression
structural and CSF measures, of progression to dementia over different intervals of follow-up. This analysis was also performed in patients designated "amyloid-negative" based on CSF A-beta. Results: The AD-signature biomarker performed better than other MRI biomarkers. Although CSF tau was better than CSF abetafor predicting dementia within 1-2 years, the AD signature performed better than all CSF measures over this relatively short-term interval, but not at longer term intervals ( 3 years). Remarkably, amyloid-negative MCI patients displayed significant AD-signature cortical thinning relative to CN. The degree of this thinning correlated with tau levels and was predictive of conversion to dementia. Conclusions: Shortterm (1-2 year) prognosis for progression to dementia relates strongly to baseline markers of neurodegeneration, with the AD-signature MRI biomarker of cortical thickness performing the best among MRI and CSF markers studied here. However, longer-term ( 3 years) prognosis may be better predicted by measures of cerebral amyloidosis. Amyloid-negative MCI patients may display atrophy in AD-specific regions, which also predicts the likelihood of future dementia conversion. While the underlying etiology of cognitive impairment is uncertain in these patients, the above findings suggest that tau-mediated neuropathology may be a contributor. Taken together, these results demonstrate the complementary nature of AD biomarkers and provide additional insight to emerging models of AD pathophysiology.