Dementia comprises a spectrum of neurodegenerative disorders marked by progressive cognitive and behavioural decline, with Alzheimer’s disease (AD) being the most prevalent form. While several genetic Show more
Dementia comprises a spectrum of neurodegenerative disorders marked by progressive cognitive and behavioural decline, with Alzheimer’s disease (AD) being the most prevalent form. While several genetic factors have been implicated in AD pathogenesis, a significant portion of heritability remains unexplained. One potential contributor to this “missing heritability” is structural variation within non-coding regions, such as variable-number tandem repeats (VNTRs). This study investigated the 40-bp VNTR located in the 3’ untranslated region of the A cohort of 799 elderly individuals from Central Italy, including AD, mild cognitive impairment (MCI), mixed dementia, and control subjects, was genotyped for the No significant association was observed between These findings suggest that while the The online version contains supplementary material available at 10.1186/s12920-026-02341-6. Show less
Protein truncating variants (PTVs) in To identify high-priority missense variants (HPVs), we applied ‘domain mapping of disease mutations’ for the 637 unique coding In this sample, PTVs and HPVs assoc Show more
Protein truncating variants (PTVs) in To identify high-priority missense variants (HPVs), we applied ‘domain mapping of disease mutations’ for the 637 unique coding In this sample, PTVs and HPVs associated with respectively a 35- and 10-fold increased risk of early onset AD and 17- and 6-fold increased risk of overall AD. The median age at onset (AAO) of PTV- and HPV-carriers was 62 and 64 years, and Our results justify a debate on whether HPV carriers should be considered for clinical counseling. The online version contains supplementary material available at 10.1186/s13024-025-00907-z. Show less