Alzheimer’s Disease (AD), the leading cause of dementia worldwide,
remains without an effective cure, largely due to an incomplete understanding of its
underlying mechanisms. Recent research highlights the central roles of amyloid β (Aβ)
and tau proteins, alongside glial cell dysfunction, in the pathogenesis of AD. This
chapter reviews advances in Aβ- and tau-related mechanisms, focusing on neuronal and
glial receptors mediating Aβ toxicity and the role of glial cells in neurodegeneration.
Early neurodegeneration in AD is marked by neuronal loss and synaptic impairment.
Despite significant progress in uncovering AD’s molecular mechanisms, the disease's
complex pathogenesis and limited diagnostic and therapeutic tools have hindered the
development of effective treatments. Comprehensive disease modelling is imperative to
clarify AD’s mechanisms and facilitate the creation of targeted therapies.
Mitochondrial dysfunction, oxidative stress, and chronic neuroinflammation emerge as
critical mediators of neuronal damage, emphasizing the multifactorial nature of AD.
This chapter reviews the interplay between inherited risk, aging, lifestyle factors, and
environmental exposures in influencing AD pathogenesis. Additionally, it will explore
how these factors contribute to the broader molecular and cellular pathways involved in
disease progression. Microglial activation and astrocytic dysfunction significantly
influence the progression of neuronal injury and synaptic loss, underscoring their
importance in AD pathogenesis. Emerging evidence underscores the importance of
understanding glial contributions to neuronal dysfunction, offering new perspectives on
disease progression and potential intervention points. The transition from early-stage
molecular alterations to widespread neuronal dysfunction and clinical decline
underscores the importance of early pathophysiological insights. Recent advancements
in understanding AD’s complex pathophysiology provide promising avenues for
enhanced diagnostics, assessing risks more accurately, and novel prevention strategies.
These discoveries bring hope for improved management and therapeutic options for the
millions affected by this debilitating condition.
Keywords: Alzheimer’s disease, AD, Molecular mechanisms, Pathophysiology alzheimer’s.
