Structural changes to the basal forebrain cholinergic system in the continuum of Alzheimer disease

In this chapter, we review evidence, derived predominantly from in vivo human MRI studies, that the basal forebrain (BF) and its projection system undergo structural changes across the continuum of Alzheimer disease (AD) progression. We examine how these changes are detectable from the earliest presymptomatic stages and continue into the prodromal and clinical phases of AD. The chapter begins with a brief overview of BF neuroanatomy before characterizing how changes to the BF and ascending cholinergic white matter projections parallel AD progression. In subsequent sections, we describe how these structural changes are exacerbated in the presence of amyloid and tau pathology, as well as in individuals at elevated genetic risk for AD. We conclude with a review of recent findings implicating the BF as a potential origin site for AD neuropathology and discuss the transsynaptic spread hypothesis of AD progression, from the BF to cortical projection targets.