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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LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies.
Why it matters
This report describes LATE-NC, a common TDP-43 proteinopathy that can mimic Alzheimer's-type dementia and was found in about 25% of brains in community-based autopsy cohorts. It shares some genetic risk factors with both frontotemporal lobar degeneration and Alzheimer's disease, but also has disease-specific mechanisms.
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A recent genome-wide association meta-analysis for Alzheimer's disease (AD) identified 19 risk loci (in addition to APOE) in which the functional genes are unknown.
Why it matters
Using fruit flies, this study screened 296 constructs targeting 54 candidate Alzheimer's risk genes and found that PTK2B acts as an early marker and in vivo modulator of tau toxicity. The human tau and PTK2B proteins interacted in vitro and co-localized with abnormal tau in Alzheimer's patient brains and transgenic tau mice, but this is early laboratory and animal work.
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67/100
A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk.
Why it matters
This meta-analysis found a significant association between the TREM2 rs75932628 variant and Parkinson's disease risk. It is about Parkinson's disease, not Alzheimer's, and does not report a treatment or cure.
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TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer's disease (LOAD) in Caucasians of European and North-American origin.
Why it matters
Earlier studies linked rare TREM2 gene variants to late-onset Alzheimer's disease in people of European origin; this study tested six such variants in African Americans (906 people with Alzheimer's and 2,487 without). One variant, p.L211P, was modestly more common in people with Alzheimer's (odds ratio 1.27, 95% CI 1.05–1.54), while p.W191X showed only a non-significant trend (odds ratio 1.35, 95% CI 0.97–1.87). This is a genetic association in one population, not a cause, and it reports no treatment, cure or prevention.
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Insulin resistance causes diminished glucose uptake in similar regions of the brain in Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2).
Why it matters
This study found that levels of a dysfunctional insulin receptor substrate in neural-derived blood exosomes differed in Alzheimer's disease and could be detected 1 to 10 years before diagnosis in a small longitudinal group. It is a biomarker study for possible early detection, not a treatment, cure, or prevention.
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Baseline levels of LD Aβ were greater for adults with mild cognitive impairment compared with adults with normal cognition (LD Aβ42, P = .05; LD Aβ40, P = .01).
Why it matters
In this small randomized trial, lipid-depleted Aβ and apolipoprotein E levels in cerebrospinal fluid differed by cognitive diagnosis and APOE genotype, and were affected by diet. The authors state these findings may provide insight, but the study does not test whether diet prevents or treats Alzheimer disease.
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In patients with sporadic ALS, we identified the repeat expansion in 236 (7·0%) of 3377 white individuals from the USA, Europe, and Australia, two (4·1%) of 49 black individuals from the USA, and six (8·3%) of 72 Hispanic individuals from the USA.
Why it matters
This study found that a C9orf72 repeat expansion is present in a substantial share of people with ALS and FTD, including many with no family history. It does not test any treatment or prevention, so it only helps identify who might carry this genetic cause.
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Ten weeks of treatment with PF-04494700 was safe and well tolerated in patients with mild-to-moderate Alzheimer disease, indicating the feasibility of a larger long-term efficacy trial.
Why it matters
This small 10-week study tested the safety and tolerability of PF-04494700 in patients with mild to moderate Alzheimer disease. It did not test whether the drug improves cognition or changes the disease course.
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The objective of our study was to assess the efficacy and safety of donepezil in young adults with Down syndrome (DS) but no evidence of Alzheimer disease (AD).
Why it matters
In young adults with Down syndrome but no Alzheimer's disease, donepezil did not significantly differ from placebo on the main cognitive measure. This study does not show that donepezil prevents Alzheimer's disease.
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The causes of late onset Alzheimer disease (LOAD) are not known but several recent lines of evidence implicate the adaptive immune system.
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A recent randomized trial demonstrated clear cerebrospinal-fluid DHA target engagement without detectable improvement in cognition or brain volume over 24 months.
Why it matters
A recent randomized trial found clear target engagement of DHA in cerebrospinal fluid but no detectable improvement in cognition or brain volume over 24 months. The authors stress this does not prove DHA lacks biological effects and does not explain why no functional benefit was seen, and they propose mitochondrial reserve as a possible modifier to be tested.
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Etalanetug presented an adequate safety and immunogenicity profile in healthy adults.
Why it matters
This was a first-in-human study in healthy volunteers, not in people with Alzheimer's disease, so it cannot yet show any effect on treating or preventing the disease. It showed the antibody was safe and well tolerated and bound its target tau in spinal fluid, which supports further testing but does not demonstrate clinical benefit.
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Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years.
Why it matters
Plasma p-tau217 was elevated in patients with corticobasal syndrome who had positive amyloid or tau PET results, helping distinguish Alzheimer's disease from other 4-repeat tauopathy syndromes. This is about improving diagnosis, not about treating, curing or preventing Alzheimer's disease.
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It is uncertain whether typical variants causing monogenic stroke are associated with cerebrovascular disease in the general population and why the phenotype of these variants varies so widely.
Why it matters
This population-based cohort study used UK Biobank data to find how common pathogenic variants in the 3 most common monogenic cerebral small vessel diseases are and whether they are associated with stroke and dementia. It is an observational genetic association study, so it cannot show that treating these variants would prevent dementia.
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Alzheimer disease comorbid pathologic characteristics are common and are associated with more rapid cognitive decline in patients with dementia with Lewy bodies (DLB); therefore, it is anticipated that plasma p-tau concentrations may have utility in assessing cognitive impairment in individuals with this disorder.
Why it matters
This cohort study measured plasma p-tau181 and p-tau231 and evaluated their associations with cognitive decline in people with probable dementia with Lewy bodies. It is an observational biomarker study and does not test any treatment, cure, or prevention.
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Kaplan-Meier analysis showed that patients with IRBD who were α-synuclein negative had lower risk for developing Parkinson's disease or dementia with Lewy bodies at 2, 4, 6, 8, and 10 years of follow-up than patients with IRBD who were α-synuclein positive (log-rank test p=0·028; hazard ratio 0·143, 95% CI 0·019-1·063).
Why it matters
In people with isolated rapid-eye-movement sleep behaviour disorder, a test called RT-QuIC detected misfolded α-synuclein in spinal fluid with 90% sensitivity and specificity, and those testing positive were more likely to later be diagnosed with Parkinson's disease or dementia with Lewy bodies. The authors say these findings would need to be repeated in other groups before the test could be used to select patients for trials of treatments targeting α-synuclein.
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However, the clinical presentation, associated factors, frequency in community-based cohorts, genetic characteristics, and cognitive trajectories associated with the quadruple misfolded proteins phenotype are not well understood.
Why it matters
In this cohort, 12.3% of individuals had quadruple misfolded proteins at death, and the APOE epsilon4 allele was associated with higher odds of this phenotype, which was linked to an aggressive course ending in severe dementia. This describes a common brain pathology pattern and its association with APOE, not a treatment or prevention.
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Tau is common in LBD and may reduce clinical diagnostic accuracy in people with DLB.
Why it matters
Pooling 49 articles, this review found Alzheimer-type tau tangles (Braak stage ≥ III) in 66% of people with dementia with Lewy bodies and 52% with Parkinson's disease dementia at autopsy. In dementia with Lewy bodies, more tau was linked to fewer hallucinations, less parkinsonism, worse cognition before death and lower accuracy of diagnosis during life. The authors conclude tau is common in these dementias and may make dementia with Lewy bodies harder to diagnose correctly during life.
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Glia have been implicated in Alzheimer's disease (AD) pathogenesis.
Why it matters
Using single-nucleus RNA sequencing, a way of reading which genes are active in individual brain cells, the study looked at brain tissue from an Alzheimer's mouse model (5XFAD) and from people with Alzheimer's. In the mice it confirmed TREM2-dependent "disease-associated microglia" and reported a previously undescribed Serpina3n+ C4b+ reactive oligodendrocyte population, but it reported "remarkably different glial phenotypes" in human Alzheimer's tissue. It is a descriptive laboratory study that does not test a treatment, and its mouse findings should not be assumed to apply to people.
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OH and RBD yielded individual and combined negative effects on disability in α-synucleinopathies, reflecting a 'malignant' phenotype of PD with early cognitive impairment and postural instability.
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Early tau deposition was elevated in women compared with men in individuals on the Alzheimer disease trajectory.
Why it matters
In this study of clinically normal older adults, women had higher tau deposition in certain brain regions than men in relation to amyloid levels. This suggests sex differences in the early brain changes of Alzheimer's disease, but it is cross-sectional and does not test any treatment.
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Mediation analyses proposed that visceral obesity contributes to deep white matter lesions through increases in proinflammatory cytokines, suggesting a pathomechanistic link.
Why it matters
This study of 1,825 adults found that a higher waist-to-hip ratio was related to more white matter hyperintensities, mainly in the deep white matter, even after adjusting for age, sex and blood pressure. It is about a risk factor and brain imaging, not a treatment or cure for Alzheimer's disease.
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We investigated the effect of crenezumab, a humanized anti-amyloid-beta (Aβ) immunoglobulin (Ig)G4 monoclonal antibody, on biomarkers of amyloid pathology, neurodegeneration, and disease progression in patients with mild-to-moderate Alzheimer's disease (AD).
Why it matters
This phase II randomized trial tested the anti-amyloid antibody crenezumab at low and high doses against placebo in patients with mild-to-moderate Alzheimer's disease. The provided findings describe the study design and biomarker endpoints but do not report whether crenezumab improved outcomes, so no treatment benefit can be concluded.
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In amyotrophic lateral sclerosis and neocortical Lewy body disease, co-pathologies associated with APOE ɛ4.
Why it matters
This study reports that, in neurodegenerative diseases, brains often carry more than one type of abnormal protein build-up ("concomitant proteinopathies"), that this becomes more common with age, and that it is linked to the APOE ɛ4 gene variant; the APOE ɛ4 link is stated specifically for ALS and neocortical Lewy body disease. The authors say this matters for clinical trials of single-target treatments aimed at tau, amyloid-β, α-synuclein or TDP-43. The record gives no prevalence figures or effect sizes, and an association with APOE ɛ4 does not show that the gene causes these build-ups.
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GBA mutations (β = 4.65; 95% CI, 1.72-7.58; P = .002), E326K (β = 3.42; 95% CI, 0.66-6.17; P = .02), and GBA variants combined as a single group (β = 4.01; 95% CI, 1.95-6.07; P = 1.5 × 10-4) were associated with a more rapid decline in MDS-UPDRS III score.
Why it matters
In 733 patients with Parkinson disease, GBA mutations and the E326K polymorphism were associated with more rapid motor decline, and a higher proportion of E326K carriers and GBA variant carriers progressed to mild cognitive impairment or dementia. These findings link genetic variants to faster progression, not to a treatment or cure.
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.
- TMEM106B, the risk gene for frontotemporal dementia, is regulated by the microRNA-132/212 cluster and affects progranulin pathways
- Dyrk1A phosphorylates alpha-synuclein and enhances intracellular inclusion formation
- Epilepsia como manifestación temprana en el espectro de la enfermedad de Alzheimer: explorando la variante epiléptica
- Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer's disease
- Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience
- Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox
- Neurobiology of ammonia
- Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins
- Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease
- Integrated single-cell analysis-based classification of vascular mononuclear phagocytes in mouse and human atherosclerosis