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. Author manuscript; available in PMC: 2017 Sep 21.
Published in final edited form as: Neuron. 2016 Sep 21;91(6):1199–1218. doi: 10.1016/j.neuron.2016.09.006

Figure 4. Alterations to Cholinergic Projections and Circuits in Dementia.

Figure 4

A. Trajectory of Alzheimer’s Disease Dementia from early to late stage (see text). Schematic representation of current concepts of cholinergic axonal retrograde death, superimposed on schematic that indicates the increasing extent of affected brain areas in blue.

B. Cellular mechanisms of cholinergic neuronal loss and subsequent disruption of target hippocampal & cortical domains. Possible mechanisms thought to underlie early loss of cholinergic projections in an animal model of AD-like dementia: Aβ induced excitotoxicity mediated by interaction with α7* nAChRs (Hascup & Hascup, 2016; Liu et al., 2016; Wu et al., 2016), and impaired neurotrophin–induced retrograde transport via Rab5 endosome enlargement (Xu et al., 2015). Images for A adapted from human brain atlas (Hawrylycz et al., 2012)