Alzheimer s Research & Therapy

Potentially modifiable lifestyle and psychological factors may influence Alzheimer’s disease (AD)-related brain pathology and cognitive function, thereby influencing cognitive resilience in late life. This cross-sectional study investigated associations and pathways between lifestyle and psychological factors related to cognitive reserve and psychological debt, AD-related biomarkers, and cognitiv…

Alzheimer's disease (AD) diagnosis remains challenging because current molecular biomarkers, though sensitive, lack spatial specificity. Radiomics offers a promising alternative by quantifying subtle microstructural alterations from routine MRI that are invisible to traditional volumetric analyses. Given that olfactory-related regions are preferentially affected in AD with olfactory dysfunction p…

Irsenontrine (E2027) is a potent and selective PDE9 inhibitor that increases cellular cGMP, essential for glutamatergic synaptic function, and was investigated as symptomatic treatment for dementia with Lewy bodies (DLB). A recent Phase 2 study suggested differences in clinical responses in irsenontrine-treated DLB patients depending on amyloid (Aβ) co-pathology. In this post-hoc CSF proteomic su…

Alzheimer’s disease (AD) is characterized by progressive cognitive impairment accompanied by behavioral disturbances and neuropsychiatric manifestations. Conventional clinic-based assessments and biomarkers provide essential diagnostic information, but these episodic measurements are limited in capturing longitudinal AD-related symptoms. Digital phenotyping has emerged as a complementary approach…

While individual associations between social determinants of health (SDoH), behavioral factors, and incident dementia have been established, the cumulative effect of multiple unfavorable SDoH and their interaction with behavioral factors remains poorly understood. We aimed to examine the independent and joint associations of SDoH and behavioral factors with incident dementia risk in middle-aged a…

Accounting for common co-pathologies such as white matter hyperintensities (WMH) may improve the prognostic performance of imaging and blood-based biomarkers for cognitive decline in Alzheimer’s disease (AD). Plasma biomarkers including p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) as well as imaging biomarkers including hippocampus volume, amyloid-β (Aβ) P…

Monoclonal antibodies targeting amyloid-β are the first approved disease-modifying treatment for Alzheimer’s disease. While amyloid-targeting therapies mitigate the progression of cognitive decline in early-stage Alzheimer’s disease, they are associated with amyloid-related imaging abnormalities (ARIA), an imaging phenomenon presenting as cerebral edema/effusion and/or hemorrhage. Redistribution …

Although protein palmitoylation has been associated with Alzheimer’s Disease (AD), it remains unclear whether or how palmitoylation of specific proteins contributes to any of the pathological features of AD. The p75 neurotrophin receptor (p75NTR) contributes to AD progression by regulating the intracellular trafficking and amyloidogenic processing of amyloid precursor protein (APP). p75NTR is pal…

Biomarker assessments increasingly inform the diagnostic evaluation and treatment decisions in Alzheimer disease (AD). However, evidence on the impact of amyloid positron emission tomography (PET) disclosure is primarily derived from studies of cognitively unimpaired trial participants with follow-up limited to 18 months. In contrast, long-term implications for individuals with cognitive concerns…