{"id":142968,"date":"2025-10-24T15:15:13","date_gmt":"2025-10-24T15:15:13","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/142968\/"},"modified":"2025-10-24T15:15:13","modified_gmt":"2025-10-24T15:15:13","slug":"alzheimers-disease-and-the-brains-eraser","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/142968\/","title":{"rendered":"Alzheimer’s disease and the brain’s ‘eraser’"},"content":{"rendered":"

\"Alzheimer\"<\/p>\n

Image Credit: ACROBiosystems <\/p>\n

September 21, 2025, marked the 32nd World Alzheimer\u2019s Day. Alzheimer\u2019s disease (AD) is the primary cause of dementia. Often linked to aging, it is a progressive neurodegenerative disorder, not a natural part of getting older.<\/strong><\/p>\n

This disorder causes neuronal damage in the brain, progressively impairing memory and cognitive function. In its advanced stages, it disrupts basic physiological functions.<\/p>\n

In recent years, progress has been made in comprehending the disease\u2019s biological mechanisms, enhancing early diagnosis, and advancing therapeutic development. Nevertheless, existing treatments provide only symptomatic relief or modestly delay disease progression, and cannot fundamentally reverse its course. The development of more effective and targeted therapies is an urgent priority.<\/p>\n

\"Progressive<\/p>\n

Progressive stages in the development of AD. Image Credit: https:\/\/doi.org\/10.3390\/nu15173688<\/a><\/p>\n

The pathological network of AD: Core and synergistic mechanisms<\/p>\n

There are two interacting cascades at the centre of Alzheimer\u2019s pathology: abnormal A\u03b2 deposition and tau hyperphosphorylation.<\/p>\n

Amyloid precursor protein (APP) is sequentially cleaved by \u03b2-secretase (BACE1) and \u03b3-secretase, producing A\u03b2 peptides that assemble into neurotoxic oligomers. Through receptors such as Nogo, these oligomers bind to neuronal membranes, resulting in calcium imbalance, mitochondrial dysfunction, and impaired synaptic transmission.<\/p>\n

At the same time, dysregulated kinases such as GSK-3\u03b2, CDK5, and MAPKs, drive tau hyperphosphorylation, causing tau to detach from microtubules and aggregate into neurofibrillary tangles. This disruption of axonal transport leads to neuronal loss and progressive cognitive deterioration.<\/p>\n

\"The<\/p>\n

The degenerative cascade in AD. Image Credit:\u00a0https:\/\/doi.org\/10.1002\/ibra.12197<\/a><\/p>\n

In addition to these primary characteristics, a variety of synergistic mechanisms contribute to AD:<\/p>\n

Cholinergic impairments, where AChE and BChE activity reduces acetylcholine insufficiency; neuroinflammation, linked to risk factors such as the APOE4 allele and TREM2-mediated microglial dysfunction, which compromises A\u03b2 clearance; synaptic dysfunction, including NPTX2 downregulation and Nogo receptor-mediated inhibition of neuronal plasticity; and metabolic abnormalities, such as progranulin deficiency and lipid metabolism disorders.<\/p>\n

Alongside A\u03b2 and tau, these mechanisms form an intricate pathological network that propels the progression of AD.<\/p>\n

\"Diagram<\/p>\n

Diagram for the pathogenesis of AD. https:\/\/doi.org\/10.1038\/s41392-024-01911-3<\/a>\u00a0<\/p>\n

Therapeutic development: From symptomatic relief to disease modification<\/p>\n