Each study has a usefulness score out of 100 (rubric version 4.0). Tap a score to see what makes it up.
Highest usefulness score first. Studies without a score come last.
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Dysfunction of immune and vascular systems has been implicated in aging and Alzheimer disease; however, their interrelatedness remains poorly understood.
Why it matters
In this work, age-dependent vascular inflammation, lymphocyte infiltration and blood-brain barrier permeability were reduced by inactivating the C3a receptor, and intracellular calcium was identified as a downstream mediator in an in vitro blood-brain barrier model. It is early laboratory work and does not show a treatment, cure or prevention for Alzheimer's disease.
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Genome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimer's disease (AD).
Why it matters
TREM2 variants are linked by genetic studies to a higher risk of Alzheimer's; this mouse study found that the R47H risk variant mainly lowered Trem2 levels in microglia (the brain's immune cells), which "resulted in decreased density of microglia in the hippocampus." Microglia with less Trem2, whether from siRNA or the R47H mice, behaved similarly, and Trem2 was important for "driving a number of the genes up-regulated in the anti-inflammatory phenotype." This is laboratory and animal work and does not establish a treatment, cure or prevention for Alzheimer's disease.
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TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding protein involved in the regulation of RNA processing.
Why it matters
This review describes evidence that misfolded TDP-43 can spread from cell to cell in a seed-dependent, self-templating, prion-like manner in diseases such as ALS, FTD, Alzheimer's disease, and LATE. It suggests this idea may guide novel therapeutic strategies for TDP-43-associated neurodegenerative diseases, but no treatment or cure is reported.
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TAR DNA-binding protein 43 (TDP-43) inclusions are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), including cases caused by G 4 C 2 repeat expansions in the C9orf72 gene (c9FTD/ALS).
Why it matters
In mice, a protein called poly(GR) produced from expanded C9orf72 repeats caused TDP-43 to clump in the cytoplasm, and antisense oligonucleotides reduced this pathology and neurodegeneration. These are animal findings and do not yet show a treatment for people with frontotemporal dementia or ALS.
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Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin.
Why it matters
In the 5XFAD mouse model, an agonistic Trem2 antibody reduced amyloid-beta deposition and improved cognition. This is animal research only and does not show that TREM2 activation would treat, cure or prevent Alzheimer's disease in people.
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The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases.
Why it matters
This is a review discussing microglial inflammatory responses and receptors including TREM2 in neurodegenerative diseases. It reports no new treatment, cure, or prevention for Alzheimer's disease.
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Alpha-synuclein (α-Syn) is a key protein involved in Parkinson's disease (PD) pathology.
Why it matters
This review compares two animal models of Parkinson's disease based on alpha-synuclein, including pre-formed fibrils and viral overexpression, and notes that fibrils trigger Lewy body-like inclusions in connected brain regions. It is a summary of models and does not test any treatment, cure or prevention.
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Macrophages play a major role in the pathogenesis of atherosclerosis.
Why it matters
This review concerns macrophage subsets in atherosclerosis, not Alzheimer's disease, so it gives no direct information about treating, curing or preventing Alzheimer's. It describes how single-cell technologies are being used to define macrophage phenotypes and functions within atherosclerotic plaques.
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Mitochondrial dysfunction and oxidative stress occur in vascular dementia (VaD), but the specific molecular mechanism regulating these events remains unclear.
Why it matters
Mice with neuron-specific overexpression of PGC-1alpha were subjected to bilateral common carotid artery stenosis to induce chronic cerebral hypoperfusion, and the study investigated whether PGC-1alpha is involved in the pathophysiology of vascular dementia. This is an animal study of vascular dementia, not a demonstrated treatment or cure for Alzheimer's disease.
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Apolipoprotein E ( APOE ) ε4 genotype is associated with increased risk of dementia in Parkinson's disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-β (Aβ), and tau pathologies.
Why it matters
In mouse models, the APOE e4 genotype was linked to greater accumulation of phosphorylated alpha-synuclein and more reactive gliosis, while APOE e2 mice showed increased survival and better motor performance. In two human Parkinson's disease cohorts, APOE e4/e4 individuals showed the fastest cognitive decline, but this is early research and does not establish a treatment for Alzheimer's disease.
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51/100
Approximately 10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer's disease (AD) both exhibit sleep disturbances, build-up of brain metabolic wastes and amyloid-β (Aβ) plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte aquaporin-4 (AQP4).
Why it matters
This review describes how the glymphatic system clears brain waste during sleep and notes that impaired glymphatic function has been implicated in both Alzheimer's disease and idiopathic normal pressure hydrocephalus. It suggests that further study could lead to new strategies, but no treatment or prevention is established.
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These new knock-in strains offer a novel and dynamic tool to study the role of APOE in AD pathogenesis in a spatially and temporally controlled manner.
Why it matters
Using new APOE knock-in mouse lines, this study found that removing APOE expression from hepatocytes did not influence early amyloid-beta deposition in the brain. This is animal research and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Here we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality of human microglia-like cells (iMGLs).
Why it matters
This laboratory study used human induced pluripotent stem cell-derived microglia-like cells to examine the effects of the Alzheimer's disease-predisposing genetic backgrounds APOE4, PSEN1ΔE9, and APPswe. It reports no treatment, cure, or prevention for people.
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Alzheimer's disease (AD) is the most common dementia in the elderly.
Why it matters
This study evaluated fecal microbiota transplantation in APP/PS1 transgenic mice as a possible treatment for Alzheimer's-like pathology. It is animal research only and does not show that this approach treats or prevents Alzheimer's disease in humans.
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Microglia adopt numerous fates with homeostatic microglia (HM) and a microglial neurodegenerative phenotype (MGnD) representing two opposite ends.
Why it matters
In mice, losing *Trem2* pushed microglia, the brain's immune cells, toward a resting "homeostatic" gene pattern, while losing *Grn* (progranulin) pushed them toward the opposite "neurodegenerative" (MGnD) pattern. Yet according to the study's title, both opposite states came with reduced brain glucose metabolism. Both genes are linked to Alzheimer's and frontotemporal dementia risk. This is mouse mechanism work; it tests no treatment and does not show the same happens in people.
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Hair growth can be induced from resting mouse hair follicles by topical application of JAK inhibitors, suggesting that JAK-STAT signaling is required for maintaining hair follicle stem cells (HFSCs) in a quiescent state.
Why it matters
This study shows that a subset of TREM2+ dermal macrophages secretes Oncostatin M, which maintains hair follicle stem cell quiescence and inhibits hair growth in mice. It concerns hair growth, not Alzheimer's disease, and reports no Alzheimer's treatment, cure or prevention.
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51/100
[F-18]-MK-6240, a novel tau positron emission tomography (PET) tracer recently discovered for the in vivo detection of neurofibrillary tangles, has the potential to improve diagnostic accuracy in the detection of Alzheimer disease.
Why it matters
In postmortem brain tissue, the tau PET tracer MK-6240 bound strongly to tangles in Alzheimer disease but not much to tau aggregates in other tau-related diseases. This is a laboratory validation study of a imaging tool, not a treatment or cure.
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CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD).
Why it matters
In a cross-sectional study, CSF sTREM2 levels rose with HIV-1 disease severity and were highest in patients with HIV-associated dementia. It does not test any treatment, cure, or prevention for Alzheimer's disease.
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Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively.
Why it matters
This study compared cerebrospinal fluid markers of neuronal damage, microglial activation, and Alzheimer's neuropathology in 121 participants grouped by cognitive status. It is a biomarker comparison study, so it does not test any treatment, cure, or prevention.
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The R47H variant of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) significantly increases the risk for late onset Alzheimer's disease.
Why it matters
In Trem2 R47H knock-in mice, the Alzheimer's risk variant impaired splicing and reduced Trem2 mRNA and protein, but this effect was not seen in humans. This is animal and cell-model work and does not demonstrate a treatment, cure, or prevention for Alzheimer's disease.
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We demonstrated that rich club organization was disrupted, with reduced structural connectivity among rich club nodes, in aMCI and d-AD patients but remained stable in SCD patients.
Why it matters
This study found that rich club organization in the brain's structural connectome was disrupted in people with amnestic mild cognitive impairment and Alzheimer's dementia but remained stable in people with subjective cognitive decline. The authors suggest this pattern could be a potential biomarker for early diagnosis, not a treatment or cure.
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TREM2 is an innate immune receptor specifically expressed in microglia.
Why it matters
This laboratory study tested whether small clumps of amyloid-beta (oligomeric Aβ 1-42) bind to TREM2, an immune sensor on the brain's microglia, using three separate binding methods, and whether this switches on TREM2 signalling (Syk and Akt) in microglia and in a reporter cell line; its title states that amyloid-beta "modulates microglial responses by binding to" TREM2. The background notes that TREM2 gene variants are linked to higher Alzheimer's risk and that the signal drawing microglia to plaques "has not been defined". It is cell and protein work with no people or treatment involved, so it does not show that changing this interaction affects Alzheimer's.
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Class 2 CRISPR-Cas systems endow microbes with diverse mechanisms for adaptive immunity.
Why it matters
The RNA-targeting CRISPR effector CasRx was engineered to work in human cells and was used to manipulate alternative splicing, alleviating dysregulated tau isoform ratios in a neuronal model of frontotemporal dementia. This is early laboratory work toward a possible platform for future therapeutic development, not a treatment tested in patients.
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Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied.
Why it matters
This study tested whether antemortem CSF biomarkers were associated with postmortem brain pathology in Lewy body disorders, using autopsy-confirmed cases and controls. It is a biomarker-pathology correlation study and does not test any treatment, cure, or prevention.
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Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases.
Why it matters
Using cryo-electron tomography in intact neurons, this study found that poly-GA aggregates from the C9orf72 repeat consist of twisted ribbons that recruit many 26S proteasomes and appear to stall their degradation. This suggests poly-GA aggregates may compromise neuronal proteostasis, but it is a laboratory structural study with no treatment tested.
From across this topic
10 of the 4,748 studies in this topic, picked by a fixed rule (a hash of each study's address), not by score or date; each page of this list shows a different 10. The same 10 appear here every time.
- Positron emission tomography tracers for synucleinopathies
- TDP-43 overexpression in the hypothalamus drives neuropathology, dysregulates metabolism and impairs behavior in mice
- PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1
- Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype
- Cortical Gray Matter Proteins Associated With Cerebral Amyloid Angiopathy in Community-Dwelling Older Adults
- Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells
- omicSynth: An open multi-omic community resource for identifying druggable targets across neurodegenerative diseases
- Fluorescence Lifetime-Based FRET Biosensors for Monitoring N Terminal Domain-Dependent Interactions of TDP-43 in Living Cells: A Novel Approach for ALS and FTD Drug Discovery
- Elevated neurofilament levels in neurological diseases
- BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases