An ¹H‐MRS framework predicts the onset of Alzheimer's disease symptoms in PSEN1 mutation carriers

Abstract

Brain metabolites measured by 1H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation.

Precuneus Failures in Subjects of the PSEN1 E280A Family at Risk of Developing Alzheimer’s Disease Detected Using Quantitative Electroencephalography

“…Although we focused on Theta and Alpha-2 bands, our analysis in different frequency bands did not show significant differences at the asymptomatic stage. Despite the results were not included in this work, we obtained differences in the Delta ([1,4) Hz) and Beta ( [13,30) Hz) bands, but only for symptomatic subjects (Appendix 1). The Gamma band, which comprises [30,50] Hz, was not evaluated given the confounding effects of the muscle artifacts [73].…”

“…• There was a lower deactivation in children and in young carriers compared with non-carriers during the encoding of information [14,89], • The FDG PET was altered around the 29 years in carriers [90] and • The Florbetapir ( 18 F) was detectable 16 years before the MCI symptoms [10], • Cortical thickness was diminished in adults asymptomatic carriers [9], • A biomarker based in magnetic resonance spectroscopy was centered also in the Precuneus [13], • Lower current source density has been detected during semantic processing [16], and • Increased connectivity was found during the encoding of visual information [19]. Our results are not only in agreement with previous results in E280a carriers, but also in concordance with those findings that had been reported the posterior regions of the DMN as the firsts region with altered activity previous to the clinical symptoms [58].…”

“…Relative power was obtained for the bands of interest: Theta [4,8) Hz and Alpha-2 [10,13) according the findings at asymptomatic stage given by Duque et al [22].…”

“…Magnetic resonance imaging in mutation carriers has demonstrated preclinical changes in cerebral thickness and volume [9]. These differences have also been identified in regional brain activity using positron emission tomography [10], functional magnetic resonance imaging [11,12] and proton magnetic resonance spectroscopy [13]. A recent study, in children in the age range of 9 to 17 years old, has identified functional and structural brain changes and abnormal levels of plasma amyloid-β-1-42, constituting the earliest biomarkers associated with E280A mutation [14].…”

Cross validation of pooling/resampling GWAS using the WTCCC data

“…This methodology is well suited to identify disease-associated genetic variants using limited and relatively small samples at a fraction of the individual genotyping cost [1]. We applied the prGWAS strategy to a unique cohort of patients with an autosomal-dominant form of Alzheimer's disease (AD) segregating a mutation in the presenilin-1 gene (PSEN1), [1][2][3][4] and identified new and previously reported loci underpinning the susceptibility to AD and/or modifying the age of onset of this dementia [1].…”