A new study explores the genetic landscape of Alzheimer’s disease and related dementias and shares insights on the identification of 42 new loci associated with Alzheimer’s Disease. Find out everything you need to know.
There are approximately 10 million new cases of Alzheimer's disease and related dementias every year, affecting 55 million people worldwide. However, genetic advances may make these diseases easier to diagnose and treat.
While much progress has been made in the management of these diseases, the exact cause or causes of Alzheimer’s disease (AD) remains unclear. This neurodegenerative, disease often described as the build-up of amyloid plaques, loss of neuron connectivity with the brain, and presentation of fiber bundles, among others, can lead to a loss of memory and cognitive skills. Currently, diagnosis is confirmed with a blood test measuring beta-amyloid proteins in cerebrospinal fluid and/or a PET brain scan.
This degenerative disease can lead to significant cognitive decline, but one study aimed to look at how genetic makeup can help us determine AD risk.
About the Study
A recent case-control, meta-analysis study led by Dr. Celine Bellenguez found 42 new AD risk loci using a two-stage genome-wide association study (GWAS). All databases were composed of donors of European ancestry. Stage I consisted of 338,440 controls and 49,275 diagnosed or proxy cases of dementia. Findings were then applied to 276,086 controls and 25,392 AD cases.
Significance of Findings
The study found that the expression of genes characterized by a higher risk of AD/ADD was highest in microglial cells. Identified loci were associated with proteins associated with regulatory pathways involved in the TNF pathway carrying out functions in cell growth, differentiation, death, and inflammation. Additionally, this study strengthened the association of tau-binding proteins, amyloid precursor proteins, and β-amyloid peptides commonly associated with AD/ADD.
These findings then culminated in the development of a genetic risk score (GRS) from findings, and a GRS was associated with increased risk in AD and AD with mild cognitive impairment progression at the 95th = probability in five and two years. Ultimately, this led to a 1.9- and 1.6-fold increase in AD/ADD predictive risk. The risk prediction was further increased when associated with APOE.
Where do we go from here?
More research is necessary to apply these findings to other ancestries of non-European descent. This study is timely as the population continues to age. However, not only did this research find more than double AD/ADD risk genetic loci, but also identify potential treatment targets that further emphasize a paradigm shift towards personalized medicine.
Bellenguez, Céline, Fahri Küçükali, Iris E. Jansen, Luca Kleineidam, Sonia Moreno-Grau, Najaf Amin, Adam C. Naj, et al. 2022. “New Insights into the Genetic Etiology of Alzheimer’s Disease and Related Dementias.” Nature Genetics 2022 54:4 54 (4): 412–36. https://doi.org/10.1038/s41588-022-01024-z.