Monoclonal antibody immunotherapies are being developed to provide disease-modifying effects in preclinical
Alzheimer’s Disease (AD). There is a pressing need for a therapeutic option that is easily administered, cost-effective, and widely available that can provide neuroprotective benefits. Angiotensin II Receptor Blockers (ARBs), a
class of antihypertensives, may offer neuroprotection in preclinical AD through anti-inflammatory and vasodilatory
pathways. Preliminary studies indicate that activation of these pathways could reduce the formation and enhance
clearance of amyloid-β (Aβ) plaques in the brain. To further investigate this, literature searches were conducted in
databases such as PubMed, NIH Clinical Trials, NEJM, and JAMA using keywords like “Alzheimer’s Disease,”
“Preclinical,” and “ARBs.” In-depth review of four clinical trials using ARBs to treat both cognitively normal older
adults and symptomatic AD patients revealed that in one symptomatic AD trial, treatment with the ARB candesartan significantly reduced Aβ accumulation in the brain. Although other clinical trials did not report significant
differences between treatment groups, they did not use the latest methodologies, such as plasma biomarkers and
cognitive scales created specifically to assess preclinical AD. We hypothesize that early treatment with ARBs may
delay preclinical pathological changes and that, in combination with monoclonal antibodies, ARBs could offer
greater therapeutic benefits than immunotherapy alone. Currently, there are no clinical trials exploring this potential
relationship, but with advances in preclinical AD detection, this is an opportune time to explore this dual therapy
for additive and synergistic effects in treating this severe neurodegenerative condition.
