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.
-
Mild cognitive impairment (MCI) and sarcopenia are prevalent age-related conditions that often coexist and share common mechanisms such as chronic inflammation, reduced neuroplasticity, and impaired muscle function.
Why it matters
This narrative review reports that resistance exercise training was linked to molecular, brain structure and cognitive improvements in older adults with mild cognitive impairment and sarcopenia, with some effects reported to persist up to 18 months. As a review of existing evidence, it does not itself test a treatment, cure or prevention.
-
Alcohol use disorders (AUDs) affect substantial populations worldwide and increase the risk of developing cognitive impairments and alcohol-associated dementia.
Why it matters
In a human cell model of neurons, astrocytes, and microglia, ethanol exposure caused immune-related gene changes, microglial activation, and increased production of a soluble form of TREM2. This is a laboratory model of alcohol-related neuroimmune dysregulation, not a finding about treating or preventing Alzheimer's disease.
-
The findings demonstrate that administration of S1P analogs cP1P and P1P at 0.1 mg/kg and 1 mg/kg significantly reduced Aβ burden by inhibiting the amyloidogenic pathway and decreasing hyperphosphorylated tau protein levels in the mouse brain.
Why it matters
In a mouse model, two sphingolipid compounds reduced amyloid burden and tau levels, calmed glial activation, and improved behavior. These are early animal findings, and it is not yet known whether they would work or be safe in people.
-
Several reports confirmed possible inadvertent iatrogenic intracranial transmission of Aβ pathology via medical and surgical procedures (1,2).A common molecular mechanism, described in prion diseases, is proposed to trigger the replication and spread of different misfolded proteins in the central nervous system (CNS), causing different neurodegenerative diseases associated with disease-specific proteins such as α-synuclein in Parkinson's disease, and amyloid-beta (Aβ) in Alzheimer's disease, and cerebral amyloid angiopathy (CAA) (3).
Why it matters
This opinion piece discusses reports that misfolded amyloid-beta can be transmitted between people through certain medical and surgical procedures, in a prion-like way, potentially causing cerebral amyloid angiopathy decades later. It argues for greater clinical, legal, and ethical awareness of this possibility, especially in younger patients with atypical brain hemorrhage.
-
The spontaneous self-assembly of proteins and nucleic acids into biomolecular condensates has been shown to ubiquitously contribute to the functional compartmentalization of the cell.
Why it matters
In molecular dynamics simulations, arginine-rich peptides accelerated the formation of harmful β-sheet structures in TDP-43 condensates, while RNAs and the HSP70 chaperone slowed it down. These are computer simulation findings about condensate aging, not a treatment tested in people.
-
In analyses of APOE ε4 carriers, dosage, and genetic risk score, APOE ε4 was associated with lower odds of fluctuating cognition and parkinsonism and higher odds of visual hallucinations.
Why it matters
In dementia with Lewy bodies, APOE ε4 was linked to higher odds of visual hallucinations, lower odds of fluctuating cognition and parkinsonism, and greater neocortical Lewy body pathology partly mediated by Alzheimer co-pathology. The authors suggest targeting APOE biology may help clarify DLB pathogenesis and inform therapeutic development, but no treatment was tested.
-
Obesity is associated with numerous adverse neural effects, including reduced neurogenesis, cognitive impairment, and increased risks for developing Alzheimer's disease (AD) and vascular dementia.
Why it matters
In mice on an obesogenic diet, deleting TLR4 in microglia/macrophages reduced neuroinflammation and cognitive problems in males, with partial protection in females. This is animal research, so it does not establish that targeting TLR4 would treat or prevent Alzheimer's disease in humans.
-
Frontotemporal dementia (FTD) is the second most common cause of dementia in patients under 65 years, characterized by diverse clinical symptoms, neuropathologies, and genetic background.
Why it matters
In induced pluripotent stem cell-derived neurons from frontotemporal dementia patients, including C9orf72 repeat expansion carriers, the cells showed TDP-43 and p62/SQSTM1 accumulation and altered synaptic function. This is a cell model of disease mechanisms, not a treatment or cure.
-
39/100
Frontotemporal dementia (FTD) encompasses a broad, clinically and neuropathologically diverse group of neurodegenerative disorders associated with changes in personality, behaviour, and/or language due to the progressive degeneration of the frontal and temporal lobes of the brain.
Why it matters
This review describes how loss-of-function mutations in the GRN gene reduce levels of progranulin and cause familial frontotemporal dementia, and notes that several therapeutic approaches are in preclinical testing and clinical trials. It summarizes progress toward potential therapies but does not report a proven treatment or cure.
-
Our findings may contribute to the growing body of knowledge on the vascular contributions to cognitive function and may help identify potential biomarkers for the early detection and intervention of AD.
Why it matters
In older adults without dementia, lower plasma von Willebrand Factor levels were linked to a faster rate of cognitive decline over time. This may help identify a potential biomarker for early detection, but it does not test any treatment or prevention.
-
We observed that GSK-3β activity was significantly upregulated in ApoE4 mice, accompanied by disruption of the insulin signaling pathway.
Why it matters
In mice with type 2 diabetes, ApoE4 worsened Alzheimer-like pathologies and cognitive impairment, and inhibiting GSK-3β with 9-ING-41 improved both in these mice. These are animal findings, and the authors suggest targeting GSK-3β may be a promising strategy, which still requires testing in humans.
-
The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type-specific effects on energy metabolism and immune pathways remain poorly understood.
Why it matters
In cell models from C9orf72 patients, microglia showed metabolic disturbances and oxidative stress that worsened with inflammation, and a three-cell culture system suggested microglia-driven changes in astrocytes make motor neurons more vulnerable. This is early laboratory work on ALS and frontotemporal dementia, not a treatment or cure for Alzheimer's disease.
-
Synaptic loss is a key factor in the cognitive decline observed during aging and in neurodegenerative diseases such as dementia, where synaptopathy plays a central role in hippocampal dysfunction.
Why it matters
In mice and cell cultures, lack of NRF2 reduced synaptic contacts and caused accumulation of ether-linked phospholipids, while the NRF2 activator 6-MSITC prevented synaptic loss. This is early animal and laboratory work, and the authors say the role of ether lipids in synaptic function and age-related decline remains poorly understood.
-
Cardiac damage and neurodegeneration simultaneously evolve in children and young adults, exposed to environmental oxidative, magnetic, motion capable, ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs).
Why it matters
This study reports magnetic nanoparticles in heart tissue of young urban residents who also had Alzheimer's, Parkinson's, or TDP-43 pathology, and describes how these particles move under magnetic fields. It proposes that exposure to ultrafine particulate matter may contribute to both heart damage and neurodegeneration starting early in life, but does not test whether treating or removing these particles changes disease.
-
39/100
Cerebral small vessel disease (cSVD) is a major contributor to stroke, dementia, and cognitive decline.
Why it matters
This review discusses the genetic architecture of cerebral small vessel disease and stroke, noting that it remains poorly understood despite large genetic studies. It does not report any treatment, cure, or prevention for Alzheimer's disease.
-
Tau mutant cortical organoids showed altered mitochondrial function and gene expression related to neuronal development, with synaptic markers and neuronal activity reduction.
Why it matters
In a 3D cortical organoid model of MAPT frontotemporal dementia, bezafibrate treatment restored mitochondrial content and rescued synaptic functionality and tau physiology. This is an in-vitro model, so it is early and preliminary and does not yet show a treatment for people.
-
39/100
Tauopathies are neurodegenerative disorders characterized by the abnormal accumulation and aggregation of hyperphosphorylated tau protein.
Why it matters
This review examines tau and tauopathies across nonhuman primate species and evaluates current and emerging primate models of tauopathy. It notes there are currently no effective treatments to prevent or slow progressive tau accumulation and that whether nonhuman primates develop human-like tau-related disorders is debated.
-
Cerebral small vessel disease (cSVD), a major contributor to stroke, cognitive decline, and vascular dementia, accounts for around 25% of ischemic strokes and significantly impacts age-related neurological disability.
Why it matters
This paper notes that cerebral small vessel disease is a major contributor to stroke, cognitive decline, and vascular dementia, accounting for around 25% of ischemic strokes. It provides background on the condition and does not report testing of any treatment, cure, or prevention for Alzheimer's disease.
-
Cerebral amyloid angiopathy (CAA) is an extremely common pathology of Alzheimer's disease (AD) included under vascular contributions to cognitive impairment and dementia (VCID).
Why it matters
In Tg2576 mice that develop cerebral amyloid angiopathy over time, this study found age-related changes in inflammatory genes and proteins, with some changes transient and others chronically altered, and differences in protein abundance based on the presence of CAA-positive vessels. These are animal findings about CAA progression and no treatment, cure or prevention is tested.
-
39/100
Dementia encompasses a range of neurodegenerative diseases (NDDs) presenting with progressive decline in memory, cognition, language and ability to complete daily tasks.
Why it matters
In serum from people with frontotemporal lobar degeneration and tauopathies, levels of C3, C3a, and properdin were elevated compared with non-demented controls, while other complement analytes did not differ significantly. Subgroup analysis found higher C3 and C3a in frontotemporal dementia and progressive supranuclear palsy but not corticobasal syndrome.
-
Alzheimer′s disease (AD) is a chronic neurodegenerative disorder that leads to memory loss and changes in mental and behavioral functions in elderly individuals.
Why it matters
In laboratory tests, compounds from the herbal medicine Gobaishi reduced amyloid-beta aggregation and, at 30 µM, pentagalloyl glucose reduced amyloid-beta-induced toxicity in SH-SY5Y cells. These are early cell-based findings, and the authors propose the compounds for further investigation rather than as a treatment.
-
Aβ 42 , TDP-43, and neurogranin show potential as blood-based biomarkers for cognitive decline and may provide insight into the pathogenesis of neurodegeneration.
Why it matters
In this cross-sectional study of 234 participants, blood levels of TDP-43 and neurogranin were elevated in dementia patients compared to those with MCI and controls. This suggests these blood markers may help distinguish dementia stages, but the study cannot show whether they predict progression over time.
-
Our findings suggest that metformin exerts therapeutic effects beyond glycemic control in the context of T2D. By mitigating neuroinflammation and modulating microglial autophagy, metformin emerges as a promising therapeutic agent for cognitive decline associated with diabetes and potentially other neurological disorders.
Why it matters
Among people with diabetes in the NACC records, metformin use was associated with better memory and executive function. In mice fed a high-fat diet, metformin reduced insulin resistance in the hippocampus (a memory area) and reversed changes in microglia, the brain's immune cells, and in cultured microglial cells it lowered inflammatory signals. The authors see metformin as a promising candidate against diabetes-related cognitive decline, though the human evidence here is observational and the mechanism work was done in mice and cells.
-
The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases.
Why it matters
This review describes evidence that SARS-CoV-2 infection may contribute to long-term neurological problems resembling ALS and frontotemporal dementia, along with increased phosphorylated TDP-43 in the central nervous system. It concludes that more research is needed to clarify this TDP-43-related neurodegeneration and to develop ways to reduce it.
-
Alterations in transactivating response region DNA-binding protein 43 (TDP-43) are prevalent in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurological disorders.
Why it matters
In mouse and human cortical astrocytes, TDP-43 dysregulation caused nucleoporin mislocalization, nuclear envelope changes, and altered nucleocytoplasmic protein transport, effects that depended on IL-1 receptor activity and NF-κB signaling and were linked to stress granule formation. Inhibiting the integrated stress response broadly reduced these changes, pointing to a convergence of proteinopathy and neuroimmune pathways in glial cells.
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.
- Cerebrovascular health impacts processing speed through anterior white matter alterations: a UK biobank study
- Quantitative synaptic alterations in the human neocortex during normal aging
- ADAM17 is the main sheddase for the generation of human triggering receptor expressed in myeloid cells (hTREM2) ectodomain and cleaves TREM2 after Histidine 157
- Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases
- Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease
- A cell therapy approach to restore microglial Trem2 function in a mouse model of Alzheimer's disease
- “D-Neuron Protection / Activation (DPA) Therapy”: New Strategy for Treatment of Neuropsychiatric Illnesses
- Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins
- Extracellular microvesicles promote microglia-mediated pro-inflammatory responses to ethanol
- Osteopontin characterizes bile duct-associated macrophages and correlates with liver fibrosis severity in primary sclerosing cholangitis