The prospects for effectively treating well-established dementia, such as Alzheimer’s disease
(AD), are slim, due to the destruction of key brain pathways that underlie higher cognitive function.
There has been a substantial shift in the field towards detecting conditions such as AD in their
earliest stages, which would allow preventative or therapeutic approaches to substantially reduce risk
and/or slow the progression of disease. AD is characterized by hallmark pathological changes such as
extracellular Aβ plaques and intracellular neurofibrillary pathology, which selectively affect specific
subclasses of neurons and brain circuits. Current evidence indicates that Aβ plaques begin to form
many years before overt dementia, a gradual and progressive pathology which offers a potential target for early intervention.
Early Aβ changes in the brain result in localized damage to dendrites, axonal processes and synapses, to which excitatory
synapses and the processes of projection neurons are highly vulnerable. Aβ pathology is replicated in a range of
transgenic models overexpressing mutant human familial AD genes (eg APP and presenilin 1). Studying the development
of aberrant regenerative and degenerative changes in neuritic processes associated with Aβ plaques may represent the best
opportunity to understand the relationship between the pathological hallmarks of AD and neuronal damage, and to develop
early interventions to prevent, slow down or mitigate against Aβ pathology and/or the neuronal alterations that leads
to cognitive impairment.
Keywords: Alzheimer’s disease, amyloid precursor protein, Aß, plaque, dystrophic neurite, selective vulnerability, transgenic
Rights & PermissionsPrintExport