Early-onset Alzheimer disease

Early-onset Alzheimer disease is a quite uncommon type of the disease that develops in relatively young individuals when they are at their 30s-early 60s and/or the diagnosis is made before they reach the age of 65.

Background

Alzheimer’s disease is one of the most common forms of dementia among the elderly, nevertheless, the disease may also affect individuals in their 40s comprising up to 5% of the ill individuals. However, making a diagnosis at this age may be quite challenging, whereas some symptoms are non-specific and may be considered related to some other circumstances such as stress and exhaustion, moreover, different disorders affecting the brain should be ruled out before the Alzheimer’s disease is confirmed.

Familial AD

One form of the Alzheimer’s disease referred to as familial (as it runs in a family) develops relatively early (before a person reaches it’s 60-ies) and, therefore, affects the younger generation. The disease occurs due to an autosomal dominant mutation in one of the genes, linked to AD – presenilin 1 (PSEN-1), presenilin 2 (PSEN-2) or amyloid beta A4 precursor protein (APP) gene. However, extremely rarely early-onset AD may be nonfamilial and develop sporadically without any explainable reason.

These mutations lead to the build-up of amyloid-beta plaques in the brain that damage it and, as a result, cause brain atrophy.

Risk factors

Having a relative who suffers/suffered from the Alzheimer disease increases one’s risks of developing the disease, especially if the disorder was caused by a recognized mutation running in a family.

Symptoms suggestive of early-onset AD

Memory loss (in this case – an inability to memorize the recent events while the memories of the past are preserved) may be one of the early symptoms of the disease. Such unusual forgetfulness is typical for Alzheimer’s and distinguishes it from the other disorders which cause memory loss. Other symptoms of the disease include some atypical signs such as vision loss, impaired speech, and altered decision-making and planning.

Later when the whole brain is affected a person experiences mood swings, the behavior changes and at some point, a person will not be able to fulfill one’s own needs and will require assistance in his/her everyday activities. For younger individuals affected by the disease, such a life-changing course of dementia is especially dramatic – a person loses a job and ability to work and gradually becomes more and more dependent on the others.

APP gene

Amyloid-beta A4 precursor protein is located on chromosome 21. The so-called Swedish and Arctic mutations of the APP gene were discovered. The Swedish mutation was linked to increased production of the amyloid-beta peptides, whereas the Arctic mutation is known to increase the production of amyloid-beta protofibrils that are considered toxic.

PSEN-1 gene

The presenilin 1 gene is found on chromosome 14. This gene encodes the synthesis of a protein which is a part of gamma- (γ-) secretase. The latter protease is involved in the cleavage of the amyloid beta-peptide. Various mutations of this allele were described, usually, their presence indicates the possible development of AD until a person becomes 50.

PSEN-2 gene

The presenilin 2 gene is located on chromosome 1. The protein synthesized according to this gene is also involved in amyloid-beta cleavage.