No abstract

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective 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 brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.

Complement proteins are integral components of amyloid plaques and cerebral vascular amyloid in Alzheimer brains. They can be found at the earliest stages of amyloid deposition and their activation coincides with the clinical expression of Alzheimer's dementia. This review will examine the origins of complement in the brain and the role of beta-amyloid peptide (Abeta) in complement activation in Alzheimer's disease, an event that might serve as a nidus of chronic inflammation. Pharmacology therapies that may serve to inhibit Abeta-mediated complement activation will also be discussed.

The β‐amyloid peptides, Aβ1‐42 and Aβ1‐40, were quantified in ventricular CSF taken daily for up to 3 weeks from six individuals with severe traumatic brain injury (TBI). There was considerable interindividual variability in the levels of Aβ peptides, but in general Aβ1‐42 levels equalled or exceeded those of Aβ1‐40. Averaging the daily totals of our trauma cohort revealed that the levels of Aβ1‐42 and Aβ1‐40 rose after injury, peaking in the first week and then declining toward control levels over the next 2 weeks. Aβ1‐42 levels were on average two to three times higher in the trauma cohort than in CSF from nontrauma samples. Compared with nontrauma samples, the Aβ1‐40/Aβ1‐42 ratio decreased about fivefold in the trauma patients, further indicative of increased Aβ1‐42 levels. The ratio remained low at all time points studied. No change was measured in the levels of β‐amyloid precursor protein during the same interval. These results suggest that Aβ1‐42 becomes elevated in the CSF after severe brain trauma.