Table 1.
Summary of the main points covered by each study and the test participants used
| Intervention | Test subject studied | Findings |
|---|---|---|
| Meningeal lymphatics | AD mouse model | Impairing meningeal lymphatics affects brain CSF influx and ISF diffusion and worsens cognitive function. Improving meningeal lymphatic function in aged mice increases brain perfusion and alleviates cognitive deficits |
| Mitochondrial homeostasis | AD human brains postmortem | Altering mitochondrial structure leads to the exacerbated production of APP-CTFs and Aβ peptides |
| Genomic instability | 5XFAD mouse model (5 AD-linked mutations) | HDAC1 knockout mice exhibit age-dependent cognitive decline, accumulation of 8-oxoG, and impaired memory. HDAC1 protects against 8-oxoG lesions in 5XFAD mice and improves cognition |
| Calcium homeostasis | J20 AD mouse model | Calcium-binding protein knockout mice show changes in their calcium buffering capacity in the subicular dendrites. Age-related decline in CB shown in non-AD mice suggests that AD causes preemptive aging |
| RBM3 (cold-shock protein) | 5XFAD mouse model | Failure to induce RMB3 parallels lost the capacity for synaptic recovery in neurodegenerative disease models. Overexpression of RMB3 restores structural synaptic plasticity and is neuroprotective in neurodegenerative disease |
| RTN3 (cold-shock protein) | 5XFAD mouse model | RBM3 binds to RTN3 mRNA and increases its translation through trans-acting effects on initiation. RTN3 overexpression increases synapse number in the wild mice and increases the survival of affected mice |
| HDL levels | AD mouse model and 3D bioengineered human arteries | Increases in HDL levels in AD mice protect against cerebrovascular dysfunction, as intravenous administration reduced Aβ levels and memory deficits. A 3D bioengineered human artery modeled vascular inflammation and was able to show that HDL functions in these vessels reduce Aβ accumulation |
| Donanemab | AD human patients | Donanemab targets Aβ peptides and can increase cognition in AD patients and decrease the tau and amyloid deposition shown on PET scans |
HDL: High-density lipoprotein, AD: Alzheimer’s disease, CSF: Cerebrospinal fluid, ISF: Interstitial fluid, APP: Amyloid precursor protein, Aβ: Beta-amyloid, HDAC: Histone deacetylases, CB: Calbindin-D28k, mRNA: Micro ribonucleic acid, PET: Positron Emission Tomography, CTFs: C-terminal fragments, 5XFAD: Mice with 5 Alzheimer’s Disease linked mutations, RTN3: Reticulon 3, RBM3: RNA-binding motif protein 3, 3D: Three-dimensional