Cerebral amyloid pathology is one of the first symptoms of Alzheimer’s neuropathology, hippocampal atrophy (the shrinking of the hippocampus, important for conscious recollection and learning), and problems with prospective cognition (the ability to remember to do something in the future, usually associated with the parietal lobe and hippocampus) (Bilgel et al., 2018). Amyloids are proteins that can lose their structure through misfolding, becoming characteristically fibrous. Sometimes, amyloids can be useful, such as in bacteria, where their fibers are used as fimbriae, helping them move around like thin flagella. In humans, they may be useful in hormone release, pigmentation, and chemical transport (Toyama & Weissman, 2011). However, amyloids are generally seen as detrimental, and amyloidosis is the disease that describes the build-up of amyloids in the body. Their fibers form plaques around cells which can impede on healthy cells, with symptoms including bruising, bleeding, internal organ swelling, external swelling, diarrhea, numbness, and weight loss (Hazenberg, 2013). If these proteins continue to midfold, they can also replicate, becoming infectious, and are known as prions.
In 2018, a team of researchers led by Murat Bilgel in Baltimore, Maryland followed 171 healthy seniors over 56 years old in a longitudinal study, and they found that those with amyloidosis or hippocampal atrophy were more likely to experience declines in verbal episodic memory, which is the recollection of saying something. When someone had both hippocampal atrophy and amyloidosis, in addition to a decline in verbal episodic memory, they were more likely to have trouble in remembering actual words (anomic aphasia), visual memory, and mental status. These results also seemed to not correlate with declines in physical function, just memory. Patients with hippocampal atrophy and amyloidosis seemed to still be able to walk, react, and interact with their physical environment, but they exhibited a lack of fluency, comprehension, and communication skills.
Current research is being done in order to treat different types of amyloidosis, such as the medication daratumumab for light chain (AL) amyloidosis, which has been approved by the FDA for its use to treat myeloma, a cancer that affects the plasma cells that help protect our bodies from infection. However, there is a need for more research in order to treat amyloidosis itself, instead of the diseases that are associated with it. If amyloidosis were to be directly addressed, there would be implications in not only AL amyloidosis, an immune cancer, but also implications for Alzheimer’s disease and more.
Citations
Bilgel M, An Y, Helphrey J, Elkins W, Gomez G, Wong DF, Davatzikos C, Ferrucci L, Resnick SM. Effects of amyloid pathology and neurodegeneration on cognitive change in cognitively normal adults. Brain. 2018 Aug 1;141(8):2475-2485. doi: 10.1093/brain/awy150. PMID: 29901697; PMCID: PMC6061788.
Franco, R., & Cedazo-Minguez, A. (2014). Successful therapies for Alzheimer's disease: why so many in animal models and none in humans?. Frontiers in pharmacology, 5, 146. https://doi.org/10.3389/fphar.2014.00146
Hazenberg BP (May 2013). "Amyloidosis: a clinical overview" (PDF). Rheumatic Diseases Clinics of North America. 39 (2): 323–45. doi:10.1016/j.rdc.2013.02.012. PMID 23597967. S2CID 215069282.
Toyama BH, Weissman JS (2011). "Amyloid structure: conformational diversity and consequences". Annual Review of Biochemistry. 80: 557–85. doi:10.1146/annurev-biochem-090908-120656. PMC 3817101. PMID 21456964.
