Expression of neurogenic markers in Alzheimer's disease: a systematic review and metatranscriptional analysis

Abstract

Alzheimer's disease (AD) is the most common form of dementia characterized by substantial neuronal loss and progressive brain atrophy. Animal studies have suggested that the process of adult neurogenesis might be altered at the earliest phases of disease onset. The relationship between AD progression and adult neurogenesis in the human brain is, however, not well understood. Here, we present a systematic review of the postmortem studies that investigated changes in human adult neurogenesis in the AD brain. We present findings from 11 postmortem studies that were identified by a systematic search within the literature, focusing on what markers of neurogenesis were used, which stages of AD were investigated, and whether the studies had any confounding information that could potentially hinder clear interpretation of the presented data. In addition, we also review studies that examined transcriptomic changes in human AD postmortem brains and reveal upregulated expression of neural progenitor and proliferation markers and downregulated expression of later neurogenic markers in AD. Taken together, the existing literature seems to suggest that the overall level of human adult neurogenesis is reduced during the later stages of AD, potentially due to failed maturation and integration of new-born neurons. Further investigations using complementary methods such as in vitro disease modeling will be helpful to understand the exact molecular mechanisms underlying such pattern of change and to determine whether neurogenesis can be an effective therapeutic target for early intervention.