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New Perspectives on the Basal Forebrain Cholinergic System in Alzheimer's Disease

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Date 2023 Apr 22
PMID 37086935
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Abstract

The basal forebrain cholinergic system (BFCS) has long been implicated in age-related cognitive changes and the pathophysiology of Alzheimer's disease (AD). Limitations of cholinergic interventions helped to inspire a shift away from BFCS in AD research. A resurgence in interest in the BFCS following methodological and analytical advances has resulted in a call for the BFCS to be examined in novel frameworks. We outline the basic structure and function of the BFCS, its role in supporting cognitive and affective function, and its vulnerability to aging and AD. We consider the BFCS in the context of the amyloid hypothesis and evolving concepts in AD research: resilience and resistance to pathology, selective neuronal vulnerability, trans-synaptic pathology spread and sleep health. We highlight 1) the potential role of the BFCS in cognitive resilience, 2) recent work refining understanding about the selective vulnerability of BFCS to AD, 3) BFCS connectivity that suggests it is related to tau spreading and neurodegeneration and 4) the gap between BFCS involvement in AD and sleep-wake cycles.

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References
1.
Gaykema R, Luiten P, Nyakas C, Traber J . Cortical projection patterns of the medial septum-diagonal band complex. J Comp Neurol. 1990; 293(1):103-24. DOI: 10.1002/cne.902930109. View

2.
Grothe M, Heinsen H, Teipel S . Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer's disease. Neurobiol Aging. 2012; 34(4):1210-20. PMC: 4058576. DOI: 10.1016/j.neurobiolaging.2012.10.018. View

3.
Beck J, Madaj Z, Cheema C, Kara B, Bennett D, Schneider J . Co-expression network analysis of frontal cortex during the progression of Alzheimer's disease. Cereb Cortex. 2022; 32(22):5108-5120. PMC: 9667180. DOI: 10.1093/cercor/bhac001. View

4.
Knipper M, Da Penha Berzaghi M, Blochl A, Breer H, Thoenen H, Lindholm D . Positive feedback between acetylcholine and the neurotrophins nerve growth factor and brain-derived neurotrophic factor in the rat hippocampus. Eur J Neurosci. 1994; 6(4):668-71. DOI: 10.1111/j.1460-9568.1994.tb00312.x. View

5.
Mintzer M, Griffiths R . Lorazepam and scopolamine: A single-dose comparison of effects on human memory and attentional processes. Exp Clin Psychopharmacol. 2003; 11(1):56-72. DOI: 10.1037//1064-1297.11.1.56. View