Neuropeptide abnormalities in patients with early Alzheimer disease

Arch Gen Psychiatry. 1999 Nov;56(11):981-7. doi: 10.1001/archpsyc.56.11.981.


Background: Deficits in somatostatin-like immunoreactivity (SLI) and corticotropin-releasing factor immunoreactivity (CRF-IR) are well recognized as prominent neurochemical deficits in Alzheimer disease (AD). The question of whether these profound neuropeptidergic deficits found in patients with end-stage disease extend into those with much earlier disease is relatively unanswered. To determine the relation between level of SLI and CRF-IR in different cerebrocortical regions to the earliest signs of cognitive deterioration in AD.

Methods: We examined SLI and CRF-IR levels in 9 neocortical brain regions of 66 elderly patients in a postmortem study of nursing home residents who had 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). Levels of CRF-IR and SLI correlated significantly with CDR, but this correlation was more robust for CRF-IR and persisted even when severely cognitively impaired patients were eliminated from analysis.

Conclusions: Although SLI and CRF-IR levels are significantly reduced in patients with severe dementia, only CRF-IR is reduced significantly in the cortices of those with mild dementia. Thus, CRF-IR can serve as a potential neurochemical marker of early dementia and possibly early AD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / physiopathology*
  • Biomarkers
  • Corticotropin-Releasing Hormone / analysis*
  • Corticotropin-Releasing Hormone / physiology
  • Entorhinal Cortex / chemistry
  • Frontal Lobe / chemistry
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neocortex / chemistry*
  • Neuropeptides / analysis*
  • Neuropeptides / physiology
  • Peptides / analysis*
  • Peptides / physiology
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Severity of Illness Index
  • Somatostatin / analysis*
  • Somatostatin / physiology
  • Temporal Lobe / chemistry


  • Biomarkers
  • Neuropeptides
  • Peptides
  • somatostatin-like peptides
  • Somatostatin
  • Corticotropin-Releasing Hormone