Basic Science and Pathogenesis.

Background: Whilst numerous studies have explored the relationship between Alzheimer's disease (AD) and diabetes, there remains significant conflicting evidence as to their relationship. Some studies suggest an increased likelihood of developing AD in individuals with diabetes, especially type 2 diabetes (T2D) and that both diseases share pathological features. In contrast, other studies indicate that T2D is more aligned with vascular cognitive impairment and dementia and associated cerebrovascular/white matter pathology.

Basic Science and Pathogenesis.

Background: The glymphatic system has been suggested as an important clearance mechanism for amyloid-β (Aβ) during sleep. Animal and cellular models have suggested this clearance mechanism involves the water-channel protein, Aquaporin-4 (encoded by the AQP4 gene), located primarily in the astrocytic end-feet. We have previously reported on the interaction between genetic variants within AQP4, sleep and cross-sectional cortical amyloid-β (Aβ) burden.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) have identified numerous genetic variants associated with Alzheimer's disease (AD) risk, but genetic variation in the onset and progression of AD pathology is less understood. Accumulation of amyloid-β (Aβ) in the brain is a key pathological hallmark of AD beginning 10 - 20 years prior to cognitive symptoms. We investigated the genetic basis of variation in age at onset (AAO) of brain Aβ by comparing the performance of polygenic scores (PGSs) based on AD risk and resilience with a Aβ-AAO trait-specific PGS.

Basic Science and Pathogenesis.

Background: Observational studies have suggested a co-occurring relationship between Alzheimer's disease (AD) and asthma. However, the aetiology and biological mechanisms underlying AD and its potential association with asthma, an autoimmune condition, remain unclear.

Method: We examine the genetic relationship between AD and asthma by analysing large-scale genome-wide association study (GWAS) summary data from international research consortia and groups.

Clinical Manifestations.

Background: Cognitive dysfunction is central to clinicopathological models of Alzheimer's disease (AD). While AD prospective studies assess similar cognitive domains, the neuropsychological tests used vary between studies, limiting potential for aggregation. We examined a machine learning (ML) data harmonisation method for neuropsychological test data to develop a harmonised PACC score for the Alzheimer's Dementia Onset and Progression in International Cohorts (ADOPIC) consortium.