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The following is a summary of “Highly prevalent geriatric medications and their effect on β-amyloid fibril formation,” published in the November 2024 issue of Neurology by Zaman et al.
Researchers conducted a retrospective study to evaluate the effects of common medications on Alzheimer’s-related β-amyloid (Aβ) fibril formation in elderly patients with Alzheimer’s disease (AD), mild cognitive impairment (MCI) and non-demented (ND).
They included patients aged ≥65 years recruited from an academic geriatric practice. Cognitive assessments were used to define disease states. Medications were categorized into 10 drug classes, and statistical analysis determined the frequency of the drugs in the cohorts, Aβ42 monomers (10 µM) and fibrillar Aβ (fAβ) were incubated for 6–48 hours with 25 µM of drugs, fAβ was prepared in a 1:10 ratio of Aβ42 to Aβ40, Aβ fibril formation was monitored using thioflavin T (Th-T) assay. Neuronal cells (N2A and SH-SY5Y) were treated with drugs (25 µM), and cell death was measured using a lactate dehydrogenase (LDH) assay.
The results showed a high prevalence (82–90%) of polypharmacy with medication classes including anti-inflammatory (65–77%), vitamins and minerals (64–72%), anti-cholesterol (33–41%), antihypertensive (35–39%), proton pump inhibitors (23–34%), and others. The LDH assay showed that Norvasc (amlodipine), Tylenol (acetaminophen), Colace (docusate), and Plavix (clopidogrel) were toxic to N2A cells, while vitamin D (cholecalciferol) and Norvasc were toxic to SH-SY5Y cells. All these drugs, except Colace, reduced the amount of Aβ fibrils when incubated with Aβ42 for 6 hours. Lipitor (atorvastatin), vitamin D, Levothyroxine, Prilosec (omeprazole), Flomax (tamsulosin), and Norvasc reduced fibril formation significantly after 48 hours of incubation with monomeric Aβ42. The disaggregation study with fAβ showed similar results for cholecalciferol (vitamin D), omeprazole (Prilosec), clopidogrel hydrogensulfate (Flomax), levothyroxine, and amlodipine (Norvasc). Drugs exhibited polyphenolic components, which are characteristic of inhibitors of Aβ fibrillation.
They concluded that polypharmacy was prevalent among older adults, and several commonly prescribed medications, including vitamin D3, Levothyroxine, Prilosec, Flomax, and Norvasc, reduce Aβ fibril formation, with Levothyroxine also preventing Aβ-mediated toxicity in neuronal cells.
Source: bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03930-7
