Rapunzel's Tangled Adventure (season 2)

• Others are risk genes that affect the body in a way that increases the chance someone will develop the disease.
• In Alzheimer’s disease, genetic mutations in any of three specific genes can cause the disease, and other risk genes either increase or decrease the risk of developing Alzheimer’s.
• Some genetic mutations or variants interact with other genetic alterations that lead to Alzheimer’s disease.

The amyloid hypothesis

• In the early 1990s, scientists proposed the amyloid hypothesis to explain how Alzheimer’s disease develops.
• These findings added strength to the amyloid hypothesis explanation of the disease.
• However, uncertainty and opposition to the amyloid hypothesis have developed over the past several decades.
• But until a clinical trial based on the amyloid hypothesis could show definitive results, uncertainty would remain.

Genetic discoveries with treatment implications

• However, a relatively small number of families have one of the three known genetic mutations that cause the disease to be passed down.
• In familial Alzheimer’s, 50% of each generation will inherit the mutated gene and develop the disease much earlier, usually from their 30s to early 50s.
• These mutated genes were found in a very large family in Colombia whose members tended to develop Alzheimer’s symptoms by their 40s.
• A genetic analysis showed that she had an additional mutation in a variant of the gene that codes for a protein called apolipoprotein E, or ApoE.

Starts and stops

• Although there is still discussion of how much slowing of decline is clinically significant, these successes provide support for the amyloid hypothesis.
• They also suggest that other strategies will be needed for optimal treatment.
• The U.S. Food and Drug Administration’s 2021 approval of the first antibody treatment for Alzheimer’s, aducanumab, sold under the brand name Aduhelm, was controversial.