AD is characterized by brain atrophy due to neuronal and synaptic loss, extracellular amyloid plaques composed of amyloid-beta peptide (A<i>β</i>), and neurofibrillary tangles of hyperphosphorylated tau protein.
Alzheimer's disease is characterized by aggregated β-amyloid and tau proteins, but the clinical presentations and patterns of brain atrophy vary substantially.
Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%).
Carriers of the GRN mutation are characterized by a variable degree of asymmetric brain atrophy, predominantly in the frontal, temporal, and parietal lobes.
Recent evidence suggests that the pathophysiology and neuropathology of Alzheimer's disease comprises more than amyloid accumulation, tau protein pathology and finally brain atrophy with dementia.
We aimed to determine the regional pattern of brain atrophy associated with the C9ORF72 gene mutation, and to determine which regions best differentiate C9ORF72 from subjects with mutations in tau and progranulin, and from sporadic frontotemporal dementia.
Rates of whole brain atrophy in GRN, and hippocampal atrophy in MAPT, were associated with age, with older subjects showing slower rates of atrophy (p = 0.01 and p < 0.001).
Together, these results indicate that brain atrophy in presymptomatic carriers of common frontotemporal dementia mutations is affected by both genetic and environmental factors such that TMEM106B enhances the benefit of cognitive reserve on brain structure.
This is the first study to show that PSEN1 rare variants collectively show a significant association with the brain atrophy in regions preferentially affected by LOAD, providing further support for a role of PSEN1 in LOAD.
We aimed to determine the regional pattern of brain atrophy associated with the C9ORF72 gene mutation, and to determine which regions best differentiate C9ORF72 from subjects with mutations in tau and progranulin, and from sporadic frontotemporal dementia.
Behavioral variant frontotemporal dementia due to C9orf72 expansion displays some phenotypic heterogeneity and may be associated with hallucinations, parkinsonism, focal dystonia, and posterior brain atrophy.