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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43/100
We present the pharmacological properties of EKZ-438, which demonstrate high selectivity for HDAC6 (>8500-fold selectivity for HDAC6 versus all other HDAC6 paralogues), low nanomolar potency (12 nM) for HDAC6, and importantly, CNS-penetrance (unbound brain-to-plasma partition coefficient [Kp,uu,brain] ≥ 0.55) and high oral bioavailability (fraction of dose absorbed [F%] = 70).
Why it matters
This study presents the pharmacological properties of a next-generation HDAC6 inhibitor, EKZ-438, showing high selectivity, CNS-penetrance, and oral bioavailability in cellular models. It concludes that selective HDAC6 inhibition is a promising therapeutic approach for potential disease modification, but this is early preclinical work and not yet a treatment.
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Higher plasma p-tau217, lower Aβ42/40, and their interaction were associated with greater Aβ-PET uptake.
Why it matters
This study found that plasma p-tau217 and Aβ42/40 may serve as accessible biomarkers of cerebral Aβ pathology and help identify individuals across the Lewy body continuum who could benefit from Aβ-targeted therapy. It is about identifying who might benefit from existing therapy, not about a new treatment, cure or prevention.
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TDP-linked proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE), are characterised by pathogenic deposits containing transactive response DNA-binding protein 43 (TDP-43) in the brain and spinal cord of patients.
Why it matters
This review discusses how the nematode Caenorhabditis elegans and its conserved TDP-43 orthologue TDP-1 are used as a genetic model to study the molecular mechanisms of TDP-43 proteinopathies. It is a review of research models and does not report or test any treatment, cure or prevention.
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FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols.
Why it matters
This study found shared and mutation-specific plasma lipid changes in frontotemporal dementia, including consistently elevated ganglioside GM3(d18:1_16:0) across GRN, MAPT and C9orf72 variants, with lipid levels correlating with disease severity. The authors propose these sphingolipids as promising biomarkers for diagnosis, subtype differentiation and disease monitoring, not as a treatment, cure or prevention.
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43/100
In PD patients, a decrease in [ 18 F]DOPA PET retention correlated with disease duration as well as CSF neurodegenerative and synaptic biomarkers but not with inflammatory biomarkers or [ 18 F]RO948 PET midbrain off-target retention.
Why it matters
In Parkinson's disease patients, lower dopamine uptake on PET correlated with longer disease duration and certain CSF markers, but there were no associations between neuroinflammatory markers and dopamine PET. This study is about Parkinson's disease, not Alzheimer's, and it reports no significant link for neuroinflammation.
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This study examined the proteome associated with TDP-43 inclusions in ALS, using mass spectrometry-based proteomic analysis of spinal cord and cerebral cortex from donors with phosphoTDP-43 positive ALS (n = 16), alpha-synuclein positive Parkinson's disease (PD, n = 8), phosphotau and beta-amyloid positive Alzheimer's disease (AD, n = 8) and age matched non-neurological controls (n = 8), comparing ALS with non-ALS conditions, spinal cord with cerebral cortex samples, and detergent-soluble with -insoluble fractions.
Why it matters
Comparing spinal cord and cerebral cortex from ALS donors, this study found different protein profiles associated with TDP-43 inclusions in each region, with RNA/DNA metabolic processes affected in spinal cord and mitochondrial and synaptic pathways in cortex. No significant increase in TDP-43 interacting proteins was found in either fraction.
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DLB with rapid cognitive decline showed greater CA1 αSYN oligomer burden (p = 0.029) and tau burden (p = 0.029) than DLB with slow decline.
Why it matters
This human brain study found that hippocampal accumulation of α-synuclein oligomers and phosphorylated tau is associated with rapid cognitive decline in dementia with Lewy bodies, and suggests that therapeutic strategies targeting α-synuclein oligomers warrant further investigation. It does not test any treatment, so it does not show a cure or prevention.
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Tauopathies are neurodegenerative diseases characterized by pathological tau protein inclusions and dementia.
Why it matters
This scoping review of 409 treatment evaluations in tauopathy mouse models found many treatments worked in mice but showed limited success in clinical trials. It identifies barriers to mouse-to-human translation, such as differences in treatment timing and lack of translatable biomarkers.
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High Resolution Image Download MS PowerPoint Slide Responders (R) and Non-Responders (NR) to lymphatic-venous anastomosis (LVA) surgery for relief of cognitive impairment show significant difference in their p-tau181/Aβ42 ratios via enzyme-linked immunosorbent assay (ELISA) of their cerebrospinal fluid (CSF).
Why it matters
Among 43 patients, the CSF p-tau181/Aβ42 ratio differed between responders and non-responders to lymphatic-venous anastomosis surgery for cognitive impairment, with a diagnostic accuracy of 0.744. This small study is about selecting patients for a specific surgery and does not establish that the surgery treats or cures Alzheimer's disease.
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), whereas the effect of region was only borderline-significant when comparing NAWM, WML peripheries and WML (p = 0.03) and non-significant for the other comparisons (p > 0.29).
Why it matters
This study found that contrast leakage accumulated within and near small vessel disease lesions, but that high contrast accumulation may mainly reflect high vascularization rather than blood-brain barrier dysfunction to the degree previously thought. It does not test any treatment, cure, or prevention.
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We included 71 DLB (76.8 ± 7.4 years old, 25 females) and 71 age- and sex-matched AD patients (and 75.2 ± 5.3 years old, 27 females).
Why it matters
This study found that patients with dementia with Lewy bodies and Alzheimer's disease both have high cerebral small vessel disease burden but differ in features, with dementia with Lewy bodies showing more enlarged perivascular spaces and deep microbleeds. It describes differences in disease features rather than testing any treatment or prevention.
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Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterized by cognitive decline, sleep disturbances, motor dysfunction, and other debilitating clinical symptoms.
Why it matters
This review states that alpha-synuclein seeding amplification assays hold promise for early and precise diagnosis of Lewy body dementia, which is often misdiagnosed. However, current limitations need to be addressed before the assay can be widely adopted as a diagnostic test.
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Neighborhood deprivation is associated with shorter survival, cognitive impairment and neurodegeneration in aging and Alzheimer's disease.
Why it matters
People with behavioral-variant frontotemporal degeneration living in the most deprived neighborhoods had shorter survival and faster decline in thinking and language than those in the least deprived neighborhoods. This shows a socioeconomic disparity in how quickly this disease progresses, not a treatment or cure.
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LLMD participants were more likely to be tau PET and Aβ PET positive than HCs.
Why it matters
Using PET and autopsy data, this study found that people with late-life mood disorders were more likely to be tau PET and amyloid PET positive and to show diverse tauopathies than controls. It suggests these mood disorders may sometimes be early states of dementia, but reports no treatment, cure or prevention.
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Recent reports suggest dysregulation of the N6-methyladenosine (m6A) RNA modification may contribute to the pathology of neurodegenerative diseases.
Why it matters
This laboratory study found that the m6A writer METTL3 may regulate chronic neuroinflammation in microglia and was increased in models and in brain tissue from people with Alzheimer's, Parkinson's, and dementia with Lewy bodies. It identifies a possible mechanism and target but does not show any treatment or cure for Alzheimer's disease.
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Vascular contributions to cognitive impairment and dementia (VCID) represent a major public health challenge in the aging population, with age-related cerebromicrovascular dysfunction playing a critical role in its development.
Why it matters
This review explores the possible role of clonal hematopoiesis of indeterminate potential in age-related cerebrovascular disease and vascular contributions to cognitive impairment and dementia. It notes that while CHIP's role in large vessel disease is well documented, its specific contributions to cerebrovascular aging and microvascular dysfunction remain poorly understood.
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Cognitive decline is a condition affecting almost one sixth of the elder population and is widely regarded as one of the first manifestations of Alzheimer's disease.
Why it matters
This study used personalized brain network models based on EEG recordings from 145 participants to link cognitive decline progression to synaptic degeneration and brain disconnection. The models revealed distinct network configurations corresponding to each patient's cognitive condition, with virtual neurodegeneration levels proportional to the severity of cognitive decline.
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Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) contribute to vascular cognitive impairment and dementia (VCID), with aging and hypertension being key risk factors.
Why it matters
In an aged hypertensive mouse model, the drug SS-31 did not significantly reduce cerebral microhemorrhage burden, though a new imaging pipeline was developed. This is preclinical animal work and does not establish any treatment, cure or prevention for dementia in humans.
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43/100
We identified a significant genome-wide association with p-S65-Ub for rs429358 (apolipoprotein E ε4 [APOE4]) and a suggestive association for rs6480922 (ZMIZ1).
Why it matters
A genome-wide association analysis found that the APOE4 variant was linked to higher levels of a marker of mitochondrial damage and greater neuropathological burden in Lewy body disease, with functional validation in mouse and human cell models. The findings concern disease risk and resilience mechanisms and do not test any treatment, cure or prevention for Alzheimer's disease.
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Our findings revealed significantly elevated CSF GAP-43 levels in individuals with AD compared to CN and MCI groups.
Why it matters
People with Alzheimer's disease had higher levels of GAP-43 in cerebrospinal fluid, and in the mild cognitive impairment group GAP-43 was linked to amyloid PET signal and tau pathology. This suggests GAP-43 could serve as a biomarker for early Alzheimer's disease, but the study does not test or provide any treatment.
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= 0.71) longitudinally. YKL-40 associations with FW and FW-corrected fractional anisotropy were null.
Why it matters
In this study, cerebrospinal fluid YKL-40 was associated with white matter hyperintensities in females but not males, both cross-sectionally and longitudinally, and was not associated with white matter microstructural measures. The authors suggest neuroinflammation may be a sex-specific driver of white matter hyperintensities in females, but the study does not test any treatment, cure, or prevention.
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Metabolic syndrome markers, such as insulin resistance and the triglyceride/HDL C ratio, correlate with early cognitive impairment.
Why it matters
This review links metabolic syndrome markers such as insulin resistance to early cognitive impairment and describes shared metabolic pathways with sarcopenia and dementia. It notes that drugs including GLP-1 receptor agonists, metformin, and SIRT1 inducers showed neuroprotective effects in animals and some preliminary clinical models, encouraging further research.
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In amnestic mild cognitive impairment (aMCI), neuroinflammation evolves during disease progression, affecting microglial function and potentially accelerating the pathological process.
Why it matters
In this ongoing double-blind placebo-controlled trial, first-stage results after three weeks showed that cognitive stimulation improved cognition, increased BDNF levels and reduced peripheral proinflammatory cytokines in people with amnestic mild cognitive impairment. The authors suggest modulating inflammatory processes may be critical in slowing disease progression, but these are early results from a trial still underway.
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Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia, often considered critical for dementia prevention.
Why it matters
This review describes an association between the gut microbiota-derived metabolite TMAO and mild cognitive impairment, and explores therapeutic strategies targeting TMAO. No effective clinical treatment for mild cognitive impairment has yet been established.
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Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson.
Why it matters
This review discusses evidence that alpha-synuclein pathology may develop in the gut and spread to the brain in Lewy body diseases, and highlights critical knowledge gaps. It concerns Lewy body diseases rather than Alzheimer's disease and reports no treatment, cure or prevention.
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.
- Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet–Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease
- Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC
- The exposome and pancreatic cancer, lifestyle and environmental risk factors for PDAC
- Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
- Opposing roles of the triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells-like transcript 2 in microglia activation
- C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation
- The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein
- Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein
- Enhanced neural activation with blueberry supplementation in mild cognitive impairment
- Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI