The role of microglia in Alzheimer’s disease: friend or foe?

Autor: T Yednock, D.B Schenk
Rok vydání: 2002
Předmět:
Zdroj: Neurobiology of Aging. 23:677-679
ISSN: 0197-4580
DOI: 10.1016/s0197-4580(02)00034-9
Popis: If attempting to understand the pathophysiology of Alzheimer’s disease (AD) were a crime drama, then microglia would have a mountain of circumstantial evidence against them at this point. Why is this so? One must first consider what is known about amyloid plaques, one of the key pathologies in AD. Beta amyloid peptide (A ) containing plaques are present in abundance in AD brain tissue [11,20]. They are known to be highly insoluble, and until recently, were presumed to be permanent entities once formed. It is, therefore, not surprising that microglia, the brain’s version of a tissue macrophage, is present in and around these structures in what has been presumed to be a futile effort to remove them. In addition, the microglia, associated with the neuritic plaques, are known to have activation markers, such as CD40 or MHCII, displayed on their surface [24]. In tissue culture, under certain circumstances, they release free radicals that can be toxic to surrounding cells [21]. As if this was not enough, a number of epidemiological studies have shown that taking NSAIDS is correlated with a reduced incidence of AD [4,9,15]. All told, it appears that it is open and shut case that microglia are guilty players in AD pathology. This general hypothesis has, in fact, been the central focus of a number of recent reviews [2,6,7,13,16,19] and is the basic theme of the article by Passinetti et al. Most efforts aimed at changing the long term course of AD is currently focused on the amyloid hypothesis. This hypothesis is based upon the testable idea that A is causative of the disease [20]. There is substantial evidence in favor of the amyloid hypothesis, which has recently been the subject of a number of reviews [22,23]. The strongest evidence in favor of it is the finding that multiple point mutations in the amyloid precursor protein (APP), presenilin I, and presenilin II, all result in overproduction of the 42 amino acid form of A . Each of these mutations cause familial forms of the disease that neuropathologically look very similar, if not
Databáze: OpenAIRE
Externí odkaz: