Causes of Alzheimer’s disease

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In most cases the definitive cause of Alzheimer’s is unknown, apart from when a genetic mutation is known to exist.

However, researchers know that a very early indication, which develops several years before symptoms first appear, is the accumulation of two proteins in the brain; the β-amyloid and hyperphosphorylated tau proteins. The amyloid protein forms sheet-like aggregates (plaques) that accumulate around the neurons, whilst the hyperphosphorylated tau proteins form aggregates inside the neurons called neurofibrillary tangles because they look like knotted up balls of yarn when viewed under a microscope. These plaques spread to different areas of the cerebral cortex, following a very similar pattern shared by all Alzheimer’s patients.

The role of these proteins in Alzheimer’s disease remains unclear but most experts believe that their aggregation into plaques interferes with normal neural function by inhibiting communication between neurons, thus preventing information from being processed normally, and eventually leading to neuron degeneration and death. In addition, other phenomena occur, such as inflammatory processes, as part of the body’s defence mechanism in response to the disease, but which could actually produce further damage.

In the rare cases classified as genetic or autosomal dominant Alzheimer’s, the cause of the disease is a genetic mutation in one of three genes: presenilin-1 (PSEN1), presenilin-2 (PSEN2) or the amyloid precursor protein gene (APP). Mutations in these genes lead to alterations in amyloid metabolism and so the protein starts to form plaques far sooner than normal.

Risk factors associated with Alzheimer’s disease

age grow up

Age. The main risk factor for developing sporadic Alzheimer’s disease is old age. The incidence and prevalence of Alzheimer’s increases with age, particularly in people aged over 65.

Woman

Females. Being female increases the risk factor given that 2 out of every 3 new cases are diagnosed in women, although it is not understood why.

family, hereditary factors

A family history of Alzheimer’s disease increases an individual’s risk of developing the condition; nevertheless, only 1 in every 200–500 cases are passed down from parent to child. The main genetic risk factor, in nonhereditary cases, is the presence of the ε4 allele of the APOE gene which increases the risk of suffering from Alzheimer’s compared to people who do not carry this allele. However, just because you have this allele it does not necessarily mean you will develop the disease as half of those carrying it will never suffer from Alzheimer’s.

Vein with cholesterol on its walls, limiting blood flow

Additionally, smoking, a sedentary lifestyle, high blood pressure, obesity and diabetes mellitus increase the risk of suffering from Alzheimer’s disease.

Mood changes, depression

What is more, other factors such as a low educational level, social isolation, depression and poor hearing also raise the likelihood of developing the disease.

Substantiated information by:

Neus Falgas Martínez
Raquel Sanchez del Valle Díaz
Soledad Barreiro Gigan

Published: 9 April 2018
Updated: 9 April 2018

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