EC Pharmacology And Toxicology

Alzheimer’s disease (AD) is the leading cause of dementia in the world [1]. Approximately 6.7 million people in the U.S. over 65 have AD, and it is estimated that as many as 13.8 million will have the disease by 2060 [2]. There are no therapies that reverse AD, and until recently, there were no disease-modifying therapies. So, how well do we understand the disease mechanism for AD? What therapies show promise? What are the major challenges facing clinicians and research scientists in terms of diagnosis and effective therapies for this dreaded disease? This brief commentary asks if the advances made in recent years will mark a turning point in the treatment of AD.

1. https://www.mayoclinic.org
2. https://pubmed.ncbi.nlm.nih.gov/
3. DJ Selkoe and J Hardy. “The amyloid hypothesis of alzheimer’s disease at 25 years”. EMBO Molecular Medicine 6 (2016): 595-608.
4. J-Z Wang., et al. “Abnormal hyperphosphorylation of tau: Sites, regulation, and molecular mechanism of neurofibrillary degeneration”. Journal of Alzheimer's Disease 1 (2013): S123-S139.
5. GT Grossberg. “Cholinesterase inhibitors for treatment of alzheimer’s disease”. Current Therapeutic Research - Clinical and Experimental 4 (2003): 216-235.
6. K Sharma. “Cholinesterase inhibitors as alzheimer’s therapeutics (Review)”. Molecular Medicine Reports 2 (2019): 1479-1487.
7. CH van Dyck. “Anti-amyloid-β monoclonal antibodies for alzheimer's disease: pitfalls and promise”. Biological Psychiatry 4 (2018): 311-319.
8. S Shcherbinin., et al. “Association of amyloid reduction after donanemab treatment with tau pathology and clinical outcomes”. JAMA Neurology10 (2022): 1015-1024.
9. M Thambisetty and R Howard. “Lecanemab trial in AD brings hope but requires greater clarity”. Nature Reviews Neurology 3 (2023): 132-133.
10. https://www.brightfocus.org/news
11. E Yasinski. “Side effects of the new alzheimer’s drugs”. MED Shadow Foundation (2024).
12. MZ Fisher. “Does medicare pay for dementia care? here’s what coverage you can expect for treatments and therapies”. Fortune Well (2024).
13. https://www.alzforum.org/therapeutics/leqembi
14. https://dian.wustl.edu/our-research/clinical-trial/
15. F Marquez and MA Yassa. “Neuroimaging biomarkers for alzheimer’s disease”. Molecular Neurodegeneration 1 (2019): 21.
16. PJ Visser., et al. “Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease”. Molecular Neurodegeneration 1 (2022): 27.
17. NJ Ashton., et al. “Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology”. JAMA Neurology3 (2024): 255-263.