New insights and emerging disease-modifying drugs for Alzheimer’s disease treatment UPorto disease Alzheimers Alzheimersdisease
Background AD is a neurodegenerative disease characterized by the progressive loss of cognitive functions and mainly affects older adults. This decline is mostly due to the aberrant accumulation of toxic protein fragments, namely amyloid-beta and tau protein. Besides, abnormalities in apolipoprotein E, particularly associated with the ε4 allele, and in the abundance of α-synuclein are also implicated.
Consequently, confusion, memory loss, behavioral changes, and apathy become evident, and eventually, basic functions are affected. Three stages of AD have been described – preclinical, mild cognitive impairment, and dementia. The central pathologic hallmarks of AD are Aβ plaques, neurofibrillary tangles, and loss of neurons.
The formation of neurofibrillary tangles of tau protein aggregates is another hallmark of AD. Abnormal phosphorylation of the tau protein reduces its affinity for microtubules and increases its susceptibility to aggregate. Thus, hyperphosphorylation of the tau protein results in its functional loss, neuronal death, loss of synapses, and dementia.
AD biomarkers Current AD diagnosis includes cognitive testing and neuroimaging, and screening of biomarkers. Identifying the disease, ideally, before symptom onset, has driven the investigation of a combination of cerebrospinal fluid biomarkers and imaging.
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