Post-mortem analysis of neuroinflammatory changes in human Alzheimer's disease

Abstract

Since the genome-wide association studies in Alzheimer's disease have highlighted inflammation as a driver of the disease rather than a consequence of the ongoing neurodegeneration, numerous studies have been performed to identify specific immune profiles associated with healthy, ageing, or diseased brain. However, these studies have been performed mainly in in vitro or animal models, which recapitulate only some aspects of the pathophysiology of human Alzheimer's disease. In this review, we discuss the availability of human post-mortem tissue through brain banks, the limitations associated with its use, the technical tools available, and the neuroimmune aspects to explore in order to validate in the human brain the experimental observations arising from animal models.

Figure 1

Microglial proliferation in post-mortem human Alzheimer’s disease brain. Representative images of the detection of Ki67 in microglial cells (Iba1⁺) by bright-field double immunohistochemistry (A) (DAB, brown, Iba1; AP, blue, Ki67) or double immunofluorescence (B) (Alexa 568, red, Iba1; Alexa 488, green, Ki67) from the temporal cortex of a patient with Alzheimer’s disease. Images adapted from [63]. Iba1, ionized calcium-binding adaptor molecule 1.