Cholinergic neuronal deficits in CADASIL.
OBJECTIVE
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.
Keverne
Jessica S
JS
Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, United Kingdom.
Low
Wee Chuang R
WC
Ziabreva
Iryna
I
Court
Jenny A
JA
Oakley
Arthur E
AE
Kalaria
Raj N
RN
D000368:Aged; D000369:Aged, 80 and over; D020532:Basal Nucleus of Meynert / Q000378:metabolism* / Q000473:pathology; D046589:CADASIL / Q000378:metabolism* / Q000473:pathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism* / Q000473:pathology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology
D020800:Receptor, Nerve Growth Factor; D002795:Choline O-Acetyltransferase