Table 3.
Major anti-amyloid AD treatments under investigation.
| Reference | Drug class | Mechanism | Key findings |
|---|---|---|---|
| Moussa-Pacha et al. (2020) | BACE1 | BACE inhibitor, reduces Aβ production. | Insignificant physiological effects, some shown to worsen cognition. Several early phase trials ongoing. |
| Hung and Fu (2017) | pTau | Derivative of methyl blue shown to inhibit tau aggregation. | Phase 2 clinical trial suggests improvement in cognition at low doses. Research ongoing. |
| Hung and Fu (2017) | pTau | Enhancing immunotherapy pTau clearance via synthetic peptide of truncated and misfolded tau. | All early phase trials. No data yet but research ongoing. |
| Hung and Fu (2017) | pTau | Microtubule stabilizing agents. | Several failed due to toxic side effects. Additional clinical trials in early phase. |
| Boada et al. (2020) | Albumin 1 Immunoglobulin Plasma Exchange | Removal of Aβ bound to albumin plasma. | New therapy. Suggests greater effect on cognition in moderate stages of AD, additional research needed. |
| Deane (2012) | RAGE | Antagonist of RAGE receptors transporting circulating Aβ to brain. | Clinical trials not effective. |
| van Dyck (2018) | Aβ | Human monoclonal anti-Aβ antibodies provide passive immunity against Aβ accumulation. | Completed trials have yielded either failed or seen non-significant outcomes. Aducanumab specifically shows more promise for improving MMSE and CDR but is in early phase testing. |
| Hung and Fu (2017) | Aβ | Aβ clearance enhanced by active immunotherapy from Aβ peptides. | Several trials discontinued due to adverse immune responses. Additional trials ongoing in early phases. |
| Hung and Fu (2017) | γ-secretase | γ-secretase inhibitors shift APP cleavage toward production of shorter, less toxic Aβ peptides. | Clinical trials discontinued due to adverse side effects. One small unpublished study suggested some improvement in cognition. |
| Hung and Fu (2017) | Intravenous Immunoglobin | A naturally occurring antibody from the plasma of healthy donors. IVIG may direct antibodies against Aβ. | No beneficial effects observed. |
| Avgerinos et al. (2018) | Intranasal Insulin | Brains affected by AD show decreased concentration of insulin and increased concentration of insulin receptors, modulated Aβ in early AD. | Some positive results in function status and ADL but no other cognitive indicators. Has been suggested that different insulin types and doses may have variable effects on different APOE patients. |
Abbreviations: BACE1, β-secretase 1; pTau, hyperphosphorylated tau; Aβ, amyloid beta; AD, Alzheimer’s disease; RAGE, receptor for advanced glycation end products; MMSE, Mini Mental State Examination; CDR, Clinical Dementia Rating; APP, Amyloid Precursor Protein; APOE, Apolipoprotein E; APOE ɛ4 allele is a risk factor for AD.