Institute for Neurodegenerative Disorders

Associations of Brain Structure and Neuropsychological Function With Artificial Intelligence Estimates of Biological Vascular Age

BACKGROUND: Accelerated vascular aging, assessed as artificial intelligence–based vascular age (AIVA), is associated with small vessel disease that may impact brain structure and neuropsychological function. METHODS: In a cross-section of Framingham Heart Study participants, AIVA...

Amyloid-beta-targeting monoclonal antibodies in early Alzheimer’s disease: a cochrane review summary and appraisal for the neurological community

Abstract Background Seven amyloid-beta-targeting monoclonal antibodies have been trialled in early Alzheimer’s disease. They differ in epitope and in how much plaque they clear; only two have traditional approval. A 2026 Cochrane Review pooled all seven as one class. We ask what...

Regulators of interferon-responsive microglia uncovered by Genome-wide CRISPRi screening

Abstract Microglia dynamically support brain homeostasis through the induction of specialized activation programs or states. One such program is the Interferon-Responsive Microglia state (IRM), which has been identified in developmental windows, aging, and disease. While the func...

Learning precise segmentation of neurofibrillary tangles from rapid manual point annotations

Accumulation of abnormal tau protein into neurofibrillary tangles (NFTs) is a pathologic hallmark of Alzheimer disease (AD). Accurate detection of NFTs in tissue samples can reveal relationships with clinical, demographic, and genetic features through deep phenotyping. However, e...

Neural signatures of major depression across the episodic memory circuitry.

In major depressive disorder (MDD), episodic memory is compromised and linked to hippocampal dysfunction, yet the underlying neural circuitry remains poorly understood. We examined the circuits supporting episodic memory and assessed its MDD-associated anatomical connectivity fin...

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures

We developed a high-content screening to investigate how Alzheimer’s disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently d...

Association of Accelerated Biological Age in Midlife with Cardiovascular Events, Dementia, and All-Cause Mortality in the Framingham Offspring Study

Accelerated biological age (ABA) better capture the aging process than chronological age (CA) and has been linked to adverse health outcomes, but long-term associations remain unclear. We modeled ABA using anthropometric and biochemical biomarkers across three examination cycles...

The impact of structural variation on Alzheimer’s disease in the Alzheimer’s disease sequencing project

Structural variants (SV), genomic alterations spanning more than 50 base pairs, can significantly impact gene expression and protein function. However, their contribution to Alzheimer’s disease (AD) remains poorly understood. Leveraging a novel SV calling pipeline, we identified...