IC‐P‐127: CSF parameters of neurodestruction and atrophy of the basal forebrain cholinergic system in mild cognitive impairment

The basal forebrain cholinergic system (BFCS) is the major source of acetylcholine for the cerebral cortex in humans and shows typical patterns of atrophy in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Lowered levels of ß-amyloid 1-42 and elevated levels of tau and phopho-tau in cerebro-spinal fluid are related to plaque and tangle formation - the neuropathological hallmarks of AD. Little is known about possible interactions of BFCS atrophy and CSF levels of amyloid or tau. We analyzed high definition 3D structural magnetic resonance imaging data from the European DTI study in dementia (EDSD) of 64 participants with the clinical diagnosis of MCI. All individuals underwent lumbar puncture for CSF analysis. We automatically extracted BFCS volumes from 3D MPRAGE data using a post mortem based mask and determined correlations between volume of the BFCS and CSF levels of amyloid ß 1-42, tau and phospho-tau. CSF levels of total tau were significantly correlated with BFCS volume of Ch4p, Ch4am_al and Ch3 subregions (Mesulam nomenclature), CSF total phospho-tau levels were significantly correlated only with the Ch3 region. Amyloid ß 1-42 levels did not show significant correlation with any of the BFCS subregions. Correlations of CSF tau/phospho-tau and BFCS atrophy agreed with neuropathological findings that neurofibrillary tangles in this area build up early in the course of AD. Furthermore, CSF levels of tau seem to better reflect the degree of atrophy of the BFCS in MCI than CSF amyloid levels.