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Cholinergic Changes in Aging and Alzheimer Disease: An [18F]-F-A-85380 Exploratory PET Study

Lagarde, Julien MD; Sarazin, Marie MD, PhD; Chauviré, Valérie MD; Stankoff, Bruno MD, PhD; Kas, Aurélie MD, PhD; Lacomblez, Lucette MD; Peyronneau, Marie-Anne PhD; Bottlaender, Michel MD, PhD

Alzheimer Disease & Associated Disorders: January-March 2017 - Volume 31 - Issue 1 - p 8–12
doi: 10.1097/WAD.0000000000000163
Original Articles

The central cholinergic system undergoes changes during the physiological process of aging and the pathologic process of Alzheimer disease (AD). We aimed to analyze the impairment of cholinergic pathways by positron emission tomography using the [18F]-F-A-85380 (FA85) tracer, which has a high affinity for nicotinic acetylcholine receptors (nAChRs). Aging was assessed by comparing young (n=10) and elderly (n=4) healthy subjects, and the pathologic process of AD was assessed by comparing elderly controls and age-matched AD patients (n=8). We measured an index of the nAChR density in the cortex and the hippocampus and the total number of FA85-binding sites by taking into account the volume changes. In AD, the nAChR density was preserved in both the cortex and hippocampus. The total estimated number of FA85-binding sites was decreased in the hippocampus despite the lack of a significant loss of volume, whereas the difference in the cortex did not withstand the adjustment for multiple comparisons despite a significant loss of volume. In contrast, in aging, the estimated number of FA85-binding sites was decreased in both the cortex and hippocampus with significant hippocampal atrophy. These findings suggest a preferential impairment of cholinergic pathways in the cortex during aging, whereas in AD, this damage predominated in the hippocampus with a potential compensatory cholinergic effect in the cortex.

*Neurology of Memory and Language Unit, Université Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Sainte-Anne hospital

Department of Neurology, Saint-Antoine hospital, APHP

§Sorbonne universités, UPMC Univ Paris 06, Inserm U 1127, and CNRS UMR 7225

Department of Nuclear Medicine, APHP, Pitié-Salpêtrière Hospital

Department of Neurology, Pitié-Salpêtrière hospital APHP, Paris

#IMIV, CEA, INSERM, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay

Department of Neurology, CHU d’Angers, Angers

**Neurospin, I2BM, DRF, CEA, Gif-sur-Yvette, France

The authors declare no conflicts of interest.

Reprints: Michel Bottlaender, MD, PhD, Neurospin, CEA, 91191 Gif-sur-Yvette, France (e-mail:

Received December 21, 2015

Accepted June 25, 2016

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