The transcriptional landscape of Alzheimer's disease and its association with Wnt signaling pathway

Abstract

Alzheimer's disease (AD) is a neurological disorder primarily affecting the elderly. The disease manifests as progressive deterioration in cognitive functions, leading to a loss of autonomy. The identification of transcriptional changes in susceptible signaling pathways has provided clues to the origin and progression of AD and has pinpointed synapse loss as the prominent event in early stages of the disease. Synapse failure represents a key pathological correlate of cognitive decline in patients. Genetics and transcriptomics studies have also identified novel genes, processes, and pathways associated with AD. This evidence suggests that a deficiency in Wnt signaling pathway contributes to AD pathogenesis by inducing synaptic dysfunction and neuronal degeneration. In the adult nervous system, Wnt signaling plays a crucial role in synaptic physiology, modulating the synaptic vesicle cycle, trafficking neurotransmitter receptors, and modulating the expression of different genes associated with these processes. In this review, we describe the general transcriptional landscape associated with AD, specifically transcriptional changes associated with the Wnt signaling pathway and their effects in the context of disease.

Keywords: Alzheimer’s disease; GWAS; RNA-seq; Synaptic function; Wnt signaling.