Neuropeptide abnormalities in patients with early Alzheimer disease

Background: Deficits in somatostatin-like immunoreactivity (SLI) and cortic otropin-releasing factorimmunoreactivity (CRF-IR) are well recognized as pr ominent neurochemical deficits in Alzheimer disease (AD). The question of w hether these profound neuropeptidergic deficits found in patients with end- stage disease extend into those with much earlier disease is relatively una nswered. To determine the relation between level of SLI and CRF-IR in diffe rent cerebrocortical regions to the earliest signs of cognitive deteriorati on in AD. Methods: We examined SLI and CRF-IR levels in 9 neocortical brain regions o f 66 elderly patients in a postmortem study of nursing home residents who h ad either no significant neuropathologic lesions or lesions associated only with AD. Patients were assessed by the Clinical Dementia Rating scale (CDR ) to have no dementia or questionable, mild, or moderate dementia, and were compared with 15 patients with severe dementia. Results: Both CRF-IR and SLI were significantly reduced in the cortices of patients with the most severe dementia, but only the levels of CRF-IR were reduced in those with mild (CDR = 1.0) and moderate dementia (CDR = 2.0). L evels of CRF-IR and SLI correlated significantly with CDR, but this correla tion was more robust for CRF-IR and persisted even when severely cognitivel y impaired patients were eliminated from analysis. Conclusions: Although SLI and CRF-TR levels are significantly reduced in pa tients with severe dementia, only CRF-IR is reduced significantly in the co rtices of those with mild dementia. Thus, CRF-IR can serve as a potential n eurochemical marker of early dementia and possibly early AD.