The cholinergic deficit coincides with A beta deposition at the earliest histopathologic stages of Alzheimer disease

Effective therapeutic intervention in Alzheimer disease (AD) will be most e ffective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the b rains of 26 subjects who had no history of cognitive loss and who were in e arly histopathologic stages of AD (average Braak stage less than II) were e xamined at autopsy to determine whether a cortical cholinergic decrement wa s associated with A beta concentration or deposition. In the superior front al and inferior temporal gyri, the choline acetyltransferase (ChAT) activit y of plaque-containing cases was significantly decreased (p < 0.05, unpaire d, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative t o plaque-free cases. In the inferior temporal gyrus, Spearman's rank correl ation analysis showed that ChAT activity had a significant inverse correlat ion with A beta concentration (p = 0.075; r = -0.3552). The results indicat e that the cholinergic deficit is established at an early histopathologic s tage of AD, before the onset of clinical symptoms.