Question

Causative mutations in which of the following genes has been described in early-onset \(\mathrm{AD}\) ? a. amyloid precursor protein, presenilin-1, presenilin- 2 b. presenilin-1, amyloid precursor protein, apolipoprotein \(\mathrm{C}\) c. presenilin-1, presenilin-2, apolipoprotein \(C\) d. apolipoprotein C, presenilin-2, amyloid precursor protein e. huntingtin, presenilin-1, presenilin-2

Short answer

Answer: The causative mutations for early-onset Alzheimer's Disease are found in the amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes.

Step-by-step solution

Recall early-onset AD genes

Recall that the primary genes associated with early-onset AD are amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2).

Compare options with genes

Compare the options provided in the exercise with the known genes for early-onset AD: a. amyloid precursor protein, presenilin-1, presenilin- 2 b. presenilin-1, amyloid precursor protein, apolipoprotein C c. presenilin-1, presenilin-2, apolipoprotein C d. apolipoprotein C, presenilin-2, amyloid precursor protein e. huntingtin, presenilin-1, presenilin- 2

Choose the correct option

Based on the information above, choose the correct option which represents the causative mutations in the genes for early-onset AD. In this case, it is option a. amyloid precursor protein, presenilin-1, presenilin- 2.

Key concepts

Amyloid Precursor Protein

Amyloid precursor protein (APP) is a crucial protein in the context of Alzheimer's Disease genetics. It is primarily involved in the formation of amyloid-beta (Aβ) peptides, which can accumulate in the brain to form plaques. These plaques are a hallmark of Alzheimer's Disease. Mutations in the APP gene can increase the production of these peptides, leading to earlier onset of Alzheimer's.

Key facts about APP:

• Plays a role in neuronal growth, survival, and post-injury repair.
• Mutations in the APP gene can result in excessive amyloid-beta production.
• APP mutations are linked with familial Alzheimer's Disease, especially in an early-onset form.

Understanding APP's role can help in grasping why targeting amyloid-beta is a popular approach in Alzheimer's research. Researchers are continually looking for ways to manage or slow the cascade of events that lead to plaque formation.

Presenilin-1 and Presenilin-2

Presenilin-1 (PSEN1) and Presenilin-2 (PSEN2) are proteins that play a pivotal role in the genetics of Alzheimer's Disease. They form part of the gamma-secretase complex, which is responsible for cleaving APP into amyloid-beta. Mutations in these genes disrupt normal processing, leading to an accumulation of amyloid-beta.

Some important points about PSEN1 and PSEN2:

• PSEN1 mutations are the most common cause of familial early-onset Alzheimer's.
• PSEN2 mutations are less common, but still significant in early-onset cases.
• Both genes contribute to improper cleavage, creating longer amyloid-beta chains that are prone to aggregation.

These mutations highlight the intricate biochemical pathways involved in Alzheimer's and underscore why targeting specific enzymes in research may offer future therapeutic benefits.

Genetic Mutations in Neurodegenerative Diseases

Genetic mutations play a critical role in many neurodegenerative diseases, including Alzheimer's. The mutations in genes such as APP, PSEN1, and PSEN2 are linked to hereditary forms of the disease, particularly early-onset Alzheimer's.

Here's how genetic mutations impact neurodegenerative diseases:

• They may cause an overproduction or improper processing of toxic proteins, like amyloid-beta in AD.
• Increased susceptibility to cell damage and death leads to the neurodegeneration seen in Alzheimer's.
• Genetic variations can influence the age of onset and the progression rate of the disease.

Understanding these mutations is critical for developing targeted therapies that aim to alter the course of the disease. As genetics research progresses, it opens the door to personalized medicine approaches, where treatments could be tailored to an individual's genetic profile.