Causes of Alzheimer’s disease

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.