ABSTRACT
OBJECTIVES: To quantify the progression of senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, and microglial activation in the cortex and white matter of patients with Alzheimer disease evaluated at both biopsy and subsequent autopsy and correlate these changes with the progression of neurologic impairment. SETTING: Academic referral center for patient with Alzheimer disease. PATIENTS: Four patients meeting the clinical criteria for Alzheimer disease, enrolled in a pilot study for the evaluation of response to intracerebroventricular administration of bethanechol chloride. The patients were followed up until death occurred and autopsy was performed. RESULTS: All 4 patients had progressive deterioration from the time of biopsy to autopsy (9-11 years). Pathological investigations showed a striking increase in the density of senile plaques and neurofibrillary tangles in 2 of 4 patients from biopsy to autopsy, and a significant increase in microglial activation in 1 of 4 cases. Severity of cerebral amyloid angiopathy varied significantly among patients, 1 of whom displayed striking amyloid deposition with associated subcortical white matter atrophy. CONCLUSIONS: These unique data demonstrate that the progressive neurologic impairment in Alzheimer disease is accompanied by a significant increase in senile plaque and neurofibrillary tangle counts in the frontal cortex and, possibly in some patients, by increased microglial cell activation. Cerebral amyloid angiopathy was associated with significant white matter disease.
Subject(s)
Alzheimer Disease/pathology , Brain/pathology , Cognition Disorders/pathology , Aged , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Amyloid beta-Peptides/analysis , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Apolipoproteins E/genetics , Bethanechol/administration & dosage , Biopsy , Brain Chemistry , Cognition Disorders/drug therapy , Cognition Disorders/genetics , Disease Progression , Humans , Injections, Intraventricular , Male , Membrane Proteins/genetics , Microglia/pathology , Middle Aged , Muscarinic Agonists/administration & dosage , Neurofibrillary Tangles/pathology , Plaque, Amyloid/pathology , Presenilin-1ABSTRACT
The purpose of this study was to assess systematically morphology of peripheral nerves from patients with human immunodeficiency virus infection (acquired immunodeficiency syndrome [AIDS] and AIDS-related complex) examined at autopsy. Sural nerve specimens were taken from 25 patients (mean age 44 years) and evaluated by routine procedures used in our laboratory. In 13 cases no detectable abnormality was seen. Twelve patients (48%) showed loss of myelinated fibers with disproportionately greater loss of large myelinated fibers. Three of these patients showed severe myelinated fiber loss; 2 had no documented symptoms and no other known predisposing factors for a peripheral neuropathy. Changes suggestive of wallerian degeneration were occasionally seen, as were epineurial and endoneurial inflammatory infiltrates. Segmental demyelination was not identified in any nerve examined. Electron microscopy revealed thickened basement membranes around small blood vessels, Schwann cells, and fibroblasts. Peripheral nerve abnormalities in patients with AIDS or ARC are frequent and their pathogenesis remains unclear.
