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Cholinergic & noradrenergic contributions to presymptomatic AD progression

Principal Investigator:
  • Nathan Spreng, McGill University
  • Alzheimer's Association

Project Overview

Alzheimer’s Association International Research Grant Program: Alzheimer’s Association Research Grant (AARG)

The development of approaches to aid early detection of the transition from healthy aging to mild cognitive impairment and Alzheimer’s disease (AD) is critically important for developing targeted strategies to halt or slow disease progression. Post-mortem studies have identified AD-related brain changes years and even decades before the age of typical AD onset, when clinically detectable cognitive changes are observed. These earliest brain changes have been identified in subcortical regions linked to specific neurotransmitter systems (e.g., the cholinergic basal forebrain and the adrenergic locus coeruleus). Whether these changes follow a predictable temporal sequence, progressing from an origin site to other subcortical and cortical regions is unknown. We will study this question using advanced neuroimaging methods in a cohort of older adults who are at elevated risk for AD, but who remain asymptomatic. The goal of this research is to track the unfolding of the AD-related pathological cascade, to identify specific staging of the degenerative processes from subcortical to cortical brain regions. This knowledge can be used to surveil for and detect neuropathological changes occurring at the very earliest disease stages, thereby expanding the window for novel treatment and intervention approaches.