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(Stroke. 2007;38:188.)
© 2007 American Heart Association, Inc.

Research Reports

Cholinergic Neuronal Deficits in CADASIL

Jessica S. Keverne, PhD; Wee Chuang R. Low, PhD; Iryna Ziabreva, PhD; Jenny A. Court, PhD; Arthur E. Oakley, CBiol Raj N. Kalaria, FRCPath

From the Institute for Ageing and Health and Department of Neuropathology, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.

Correspondence to Raj N. Kalaria, Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, United Kingdom. E-mail r.n.kalaria{at}ncl.ac.uk

Background and Purpose— Previous evidence from MRI and acetylcholinesterase histochemistry suggests cholinergic fibers are affected in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Methods— As a measure of cholinergic function, we assessed choline acetyltransferase (ChAT) activities in the frontal and temporal neocortices and the immunocytochemical distribution of ChAT and p75 neurotrophin receptor (P75^NTR) by in vitro imaging in the nucleus basalis of Meynert of CADASIL subjects.

Results— ChAT activities were significantly reduced by 60% to 70% in frontal and temporal cortices of CADASIL cases, as were ChAT and P75^NTR immunoreactivities in the nucleus basalis.

Conclusions— Our findings suggest cholinergic neuronal impairment in CADASIL and implicate cholinomimetic therapy for subcortical vascular dementias.

Key Words: CADASIL • cholinergic neurones • cognitive impairment • small vessel disease • vascular dementia