Microglial interleukin-1 alpha expression in human head injury: correlations with neuronal and neuritic beta-amyloid precursor protein expression

Abstract

Activated microglia containing IL-1 alpha-immunoreactive (IL-1 alpha +) product were increased 3-fold in number in the acute phase following head injury, a risk factor for later development of Alzheimer's disease, and this increase was correlated with a 7-fold increase in the number of neurons with elevated beta-amyloid precursor protein (beta-APP) levels (R = 0.78; P < 0.05). Furthermore, clusters of beta-APP+ dystrophic neurites present in these patients were invariably associated with activated IL-1 alpha + microglia. These findings suggest that early overexpression of IL-1 alpha and beta-APP is a priming event for later neuropathological changes evident at end stages of Alzheimer's disease.

Fig. 1

A: numbers (mean ± S.E.M.) of IL-1α⁺ microglia and β-APP⁺ neurons in mesial temporal lobe tissue sections from 7 head-injured and 6 control patients.*P < 0.05; **P < 0.01. B: correlation between numbers of activated IL-1α⁺ microglia and β-APP⁺ neurons in 7 head-injured patients (R = 0.78; P < 0.05).

Fig. 2

β-APP⁺ (red) neurites and IL-1α⁺ (brown) microglia in dual-labeled immunohistochemically reacted tissue sections from mesial temporal lobe of control (A), head-injured (B), and Alzheimer's (C) patients. Bar = 15 μm.