Early onset Alzheimer’s disease is a less common form of dementia, typically affecting individuals under 65. It accounts for 5% to 10% of all Alzheimer’s cases. Unlike the more prevalent late-onset form, early onset Alzheimer’s often has a strong genetic component. Understanding this genetic basis helps differentiate it and explains its progression.
Key Genes Linked to Early Onset Alzheimer’s
Early onset Alzheimer’s disease is linked to changes in three genes: Amyloid Precursor Protein (APP), Presenilin 1 (PSEN1), and Presenilin 2 (PSEN2). The APP gene, on chromosome 21, provides instructions for a protein involved in neuron growth and repair. Mutations in APP can lead to increased production of amyloid-beta protein.
The PSEN1 gene, on chromosome 14, processes proteins like APP as part of the gamma-secretase complex. PSEN1 mutations are the most frequent genetic cause of early onset Alzheimer’s, accounting for most familial cases. The PSEN2 gene, on chromosome 1, also contributes to the gamma-secretase complex. PSEN2 mutations are less common but also contribute to the disease’s development.
How Genetic Changes Lead to Alzheimer’s
Mutations in APP, PSEN1, and PSEN2 genes directly influence amyloid precursor protein processing. The APP protein is normally cleaved by enzymes into smaller fragments. When APP mutations occur, this cleavage is altered, leading to an overproduction of amyloid-beta 42 (Aβ42).
Mutations in PSEN1 and PSEN2 affect gamma-secretase, an enzyme complex that cuts the APP protein. These genetic changes cause gamma-secretase to generate an increased amount of Aβ42. This overabundance of Aβ42 leads to its aggregation, forming insoluble clumps called amyloid plaques in the brain.
These plaques disrupt communication between brain cells and initiate detrimental events. The accumulation of amyloid plaques triggers abnormal phosphorylation and aggregation of tau protein, forming neurofibrillary tangles inside neurons. These tau tangles impair neuronal transport systems, leading to widespread brain cell damage and death, hallmarks of Alzheimer’s disease.
Inheritance Patterns and Genetic Testing
Early onset Alzheimer’s linked to APP, PSEN1, or PSEN2 mutations typically follows an autosomal dominant inheritance pattern. This means inheriting only one copy of the mutated gene from a parent can lead to the disease. Each child of an affected parent has a 50% chance of inheriting the mutated gene and developing the condition.
Genetic testing can identify mutations in APP, PSEN1, and PSEN2 genes. It is considered for individuals with symptoms or a family history of early onset Alzheimer’s. Pre-symptomatic testing is also an option for at-risk individuals without symptoms. Genetic counseling is recommended before and after testing. A genetic counselor provides information on test implications, discusses emotional aspects of knowing one’s genetic status, and helps families navigate decisions.
Living with Early Onset Alzheimer’s and Genetic Risk
An early onset Alzheimer’s diagnosis presents unique emotional and practical challenges due to its younger age of occurrence. Individuals may be in their careers or raising families, leading to significant disruptions in daily life and future planning. Support groups offer a valuable resource for sharing experiences and coping strategies. Counseling can also assist in processing the diagnosis and managing its psychological impact on both the person with the disease and their caregivers.
Research explores new treatments and interventions for genetically linked Alzheimer’s. Scientists investigate therapies to reduce or clear amyloid plaques from the brain. Other research targets tau pathology, developing methods to slow or prevent neurofibrillary tangles. These studies aim to improve quality of life and potentially alter the disease course for those affected by early onset Alzheimer’s.