Mind and memory: a multidisciplinary exploration of Alzheimer's disease.

Abstract

AD is a neurodegenerative disease and is one of the leading causes of death globally, accounting for more than 4% of deaths in 2016. The dementia-related death rate from AD was more than 45 per 100,000 in a 2013 European study. The prevalence of atypical AD, most common in individuals under 65 years of age, ranges from 15-65/100,000, with some patients experiencing visual or motor difficulties, executive dysfunction, and other symptoms.

The pathogenesis of AD is linked to the presence of clusters of extracellular amyloid beta (Aβ) protein, known as neuritic plaques, and tangles of hyperphosphorylated tau proteins. These plaques are formed from amyloid precursor protein (APP) by the action of enzymes, while neurofibrillary tangles consist mainly of hyperphosphorylated tau protein.

The relationship between Aβ and tau is synergistic in neurotoxicity, with evidence that Aβ can trigger the formation of tau tangles. Biometals such as iron, copper and zinc have also been linked to AD, with dysregulation of these metals contributing to nervous system toxicity.

Genetic factors, including the APOE gene and mutations in the APP, PSEN-1, and PSEN-2 genes, also play an important role in AD. The presence of the APOE ε4 allele significantly increases the risk of developing the disease. Mutations in the APP gene are associated with an accumulation of Aβ, while mutations in PSEN-1 and PSEN-2 affect Aβ production.

Clinical manifestations include memory loss, depression, anxiety, language disorders and other cognitive and behavioral changes. The phase of AD varies from preclinical to severe, progressively affecting the patient's daily functioning.

Diagnosis combines clinical assessment, neuropsychological tests and biomarkers such as tau protein, Aβ42 and brain imaging. Treatment involves medications such as acetylcholinesterase inhibitors and memantine, as well as therapies being studied that target Aβ proteins. Healthy lifestyles, such as physical activity and diet, also play an important role in preventing and treating AD.