From the Guidelines
There is a strong link between Down syndrome and Alzheimer's disease, with at least 50% of adults with Down syndrome aged 60 years and older developing clinical evidence of dementia.
Relationship Between Down Syndrome and Alzheimer's Disease
- The underlying genetic link between trisomy 21 and Alzheimer’s disease has been convincingly established, with the triplication of chromosome 21 containing genes that play a role in the development of Alzheimer’s disease 1.
- By age 40 years, all adults with Down syndrome exhibit some degree of neuropathologic defects postmortem that meet the criteria for Alzheimer’s disease, although the development of clinical Alzheimer’s disease is variable 1.
- The overexpression of the gene coded on chromosome 21 for amyloid precursor protein leads to the excessive production of b-amyloid, which is key to the pathogenesis of Alzheimer’s disease 1.
- Down syndrome is the only genetically inherited form of intellectual disability that has been indisputably linked to the risk of early development of Alzheimer’s disease, with other genes coded on chromosome 21 also potentially contributing to the early emergence of dementia and accelerated aging 1.
From the Research
Relationship Between Down Syndrome and Alzheimer's Disease
The relationship between Down syndrome and Alzheimer's disease is complex and has been extensively studied. Key findings include:
- Virtually all adults with Down syndrome show the neuropathological changes of Alzheimer's disease by the age of 40 years 2
- The extra copy of the APP gene located on chromosome 21 is a significant contributor to the development of Alzheimer's disease in individuals with Down syndrome 3, 4
- Amyloid-β accumulates in the brain across the lifespan of people with Down syndrome, providing a unique opportunity to understand the temporal progression of Alzheimer's disease 2
Genetic Signatures and Pathways
Research has identified several genes that may be important to both Down syndrome and Alzheimer's disease, including:
- ACSM1, APBA2, APLP1, BACE2, BCL2L, COL18A1, DYRK1A, IK, KLK6, METTL2B, MTOR, NFE2L2, NFKB1, PRSS1, QTRT1, RCAN1, RUNX1, SAP18, SOD1, SYNJ1, S100B 3
- These genes are involved in various pathways, including APP processing, Tau post-translational modification, and network connectivity 3
Clinical Implications and Research Priorities
Studies have highlighted the need for:
- Target identification and drug development 5
- Clinical and pathological staging 5
- Cognitive assessment and clinical trials 5
- Partnerships and collaborations to deliver effective disease-modifying treatments 5
- The development of preventative treatments for Alzheimer's disease in individuals with Down syndrome, which must start well before the onset of symptoms 4