How early does the cholinergic enzyme loss occur in AD?

• Early studies (1970’s, 1980’s) revealed severe loss of ChAT enzyme activity

• Davis (1999): no loss of ChAT activity in cortical regions in MCI (CDR = 0.5) and ‘mild AD’ as determined by postmortem CDR

• Tiraboschi et al. (2000) similar findings, studied frontal lobe only

• Levey and colleagues: little or no loss of basal forebrain cholinergic neurons in MCI

• DeKosky (2001) preservation of cortical and hippocampal ChAT in MCI and mild AD

• So early symptoms of AD might not be caused by cholinergic enzyme deficits, though cholinergic dysfunction is present

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