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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GRN mutations cause progranulin haploinsufficiency, which eventually leads to frontotemporal dementia (FTD-GRN).
Why it matters
This first-in-human phase 1/2 trial tested PR006, an investigational gene therapy delivering the granulin gene using an AAV9 vector, in patients with frontotemporal dementia caused by GRN mutations. Non-clinical studies showed the therapy transduced patient-derived neurons and improved pathologies in mice, and the trial is ongoing to assess safety and tolerability.
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The main findings demonstrated an association between serum GFAP level and post-mortem tau pathology (β = 12.85; P < 0.001) that was independent of amyloid deposits (β = 13.23; P = 0.02).
Why it matters
This cohort study found that serum GFAP levels were associated with post-mortem tau pathology independently of amyloid deposits, and were also associated with hippocampal sclerosis and argyrophilic grain disease. The authors state that further research is needed to replicate and validate these results in diverse populations, so this is biomarker and mechanistic evidence rather than a treatment or cure.
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Glymphatic failure may precede amyloid pathology, and predicts amyloid deposition, neurodegeneration, and clinical progression in AD.
Why it matters
In participants with Alzheimer's disease dementia, mild cognitive impairment and normal controls, a lower ALPS index was associated with faster amyloid PET burden change, higher risk of amyloid-positive transition and clinical progression, and faster cognitive decline, with the associations fully mediated by amyloid PET and brain atrophy. The findings suggest glymphatic failure may precede amyloid pathology and predict progression, but no treatment, cure or prevention is tested.
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In a proportion of patients, dementia with Lewy bodies (DLB) is associated with Alzheimer disease (AD) copathology, which is linked to accelerated cognitive decline and more extensive cortical atrophy.
Why it matters
In this trial of neflamapimod in people with dementia with Lewy bodies, improvements were greater in participants with lower baseline plasma phosphorylated tau, with significant improvement over placebo on some measures in that group. It is about a subgroup response in dementia with Lewy bodies, not about treating, curing or preventing Alzheimer disease.
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The Olink Proteomics panel of inflammation markers ( https://www.olink.com/products/inflammation/ ) will be used to evaluate 92 proteins associated with inflammatory diseases and related biological processes.
Why it matters
This record describes an ongoing randomised, open-label trial of EGb 761 in people with mild cognitive impairment, testing its antioxidant and anti-inflammatory effects on blood markers and whether these relate to cognitive decline. Inflammation is being measured with a panel of 92 proteins. Results are not reported in this record.
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Among 16 enrolled participants, the mean (SD) age was 32.6 (4.4) years; 9 participants were women, and 7 were men.
Why it matters
This phase 1b trial in 16 adults with Down syndrome found the ACI-24 vaccine was safe and produced antibodies in some participants. It is an early safety and immune response study and does not show that the vaccine treats, cures, or prevents Alzheimer's disease.
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Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear.
Why it matters
In people with autosomal-dominant Alzheimer disease, faster increases in soluble TREM2 in spinal fluid were linked to slower amyloid buildup, suggesting a possibly beneficial role for TREM2. This is an observational biomarker study and does not test any treatment, cure, or prevention.
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Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood.
Why it matters
Across 2,269 people in two cohorts (King's College London and Sweden's BioFINDER), a blood marker of nerve-cell damage, plasma neurofilament light (NfL), was raised in all cortical neurodegenerative disorders, ALS and atypical parkinsonian disorders. That means a high level signals neurodegeneration in general, not Alzheimer's in particular. The authors found it useful for specific questions, such as spotting dementia in people with Down syndrome or separating dementia from psychiatric illness, and found it worked best for ruling out neurodegeneration, provided age-appropriate cut-offs are used. It is a diagnostic test study and does not treat or prevent any of these conditions.
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Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause.
Why it matters
This genetic study found that periventricular and deep white matter hyperintensities have different genetic underpinnings. It is observational and does not test any treatment, cure or prevention for dementia.
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Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late-onset Alzheimer's disease (AD).
Why it matters
In mice, losing TREM2 function increased the early seeding of amyloid plaques and reduced microglial clustering and ApoE around new plaques. This suggests TREM2 and microglia affect how amyloid plaques begin to form, but it is animal and human tissue work, not a treatment.
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After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (β = 0.41; 95% CI, 0.27-0.55; P Conclusions and relevance We provide robust evidence of a stronger association between APOE-ε4 and CSF tau levels among women compared with men across multiple independent data sets.
Why it matters
Pooling data from 10 cohort studies (1,798 people with spinal-fluid tests, mostly white, average age 70), the authors found that the APOE-ε4 gene variant was more strongly linked to spinal-fluid tau levels in women than in men. In a separate group of 5,109 people examined after death, ε4 was "not differentially associated" with tau tangles in the brain, so the sex difference appeared in fluid tau measured during life but not in tangles seen at autopsy. This is an observational association. It does not predict an individual's risk or point to any treatment.
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Among military veterans, mTBI is associated with 56% increased risk of PD, even after adjusting for demographics and medical/psychiatric comorbidities.
Why it matters
In this cohort of veterans, traumatic brain injury of all severities, including mild TBI, was associated with a higher risk of later Parkinson disease. This is about Parkinson disease risk, not Alzheimer's disease, and it does not show that brain injury causes Parkinson disease.
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We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD.
Why it matters
Pooling genome-wide association data (192,886 cases and controls in total), this study found that genetic variants linked to frontotemporal dementia (FTD) overlap strongly with those for several immune diseases: up to 270-fold enrichment with rheumatoid arthritis and 160- to 180-fold with ulcerative colitis, type 1 diabetes and celiac disease. The overlap was weaker or narrower in related conditions (PSP, CBD) and minimal in ALS, and the authors locate it "particularly within the HLA region." They conclude that immune dysfunction "may contribute to FTD risk" for a subset of patients. This is a genetic association in FTD, not Alzheimer's disease, and it does not test any treatment.
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This study showed that flutemetamol injection labeled with radioactive fluorine 18 was safe and had high sensitivity and specificity in an end-of-life population.
Why it matters
This phase 3 trial found that flutemetamol injection labeled with radioactive fluorine 18 was safe and had high sensitivity and specificity for detecting neuritic plaque density in an end-of-life population. When scans were interpreted with computed tomography images, sensitivity and specificity improved for most readers but the differences were not significant.
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71/100
Using stratification with simply assessed markers, it is now not only possible, but practical to include patients with RBD in neuroprotective trials against Parkinson disease, multiple system atrophy, and dementia with Lewy bodies.
Why it matters
In people with idiopathic REM sleep behavior disorder, the risk of developing a neurodegenerative synucleinopathy was 30% at 3 years and 66% at 7.5 years. Certain markers (advanced age, olfactory loss, abnormal color vision, subtle motor dysfunction, and nonuse of antidepressants) identified higher risk, and combining markers increased risk by 200%, which could help select patients for future neuroprotective trials.
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We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88).
Why it matters
This multicenter study found that mutations in the GBA1 gene were significantly associated with dementia with Lewy bodies and with Parkinson's disease with dementia. This identifies a genetic risk factor for these conditions but does not provide a treatment, cure or prevention.
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No significant differences were noted between the two treatments in patients with PDD (3·6 with memantine vs 3·8 with placebo, -0·1 [-0·6 to 0·3]; p=0·576) or in the total population (3·5 with memantine vs 3·8 with placebo, -0·3 [-0·7 to 0·1]; p=0·120).
Why it matters
Memantine showed no significant difference from placebo on the main outcome in patients with Parkinson's disease dementia or in the total population. Some neuropsychiatric improvement was seen in dementia with Lewy bodies, but most cognitive, daily living, and caregiver burden scores showed no significant differences between treatments.
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Plasma p-tau217 is a prognostic marker for identifying individuals who will develop cognitive impairment within ten years.
Why it matters
In cognitively unimpaired individuals followed for a mean of 5.65 years, elevated plasma p-tau217 predicted progression to mild cognitive impairment, with higher rates in those who were also amyloid positive. Adding plasma Aβ42/40 status did not improve prediction, and all individuals with abnormal tau PET in a temporal region progressed to mild cognitive impairment.
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70/100
In this nationwide population-based study, SGLT2i use significantly reduced the risks of neurodegenerative disorders in patients with type 2 diabetes independent of various factors including comorbidities and bioclinical parameters.
Why it matters
In this nationwide population-based study of 358,862 people with type 2 diabetes, SGLT2 inhibitor use was associated with reduced risks of Alzheimer disease, vascular dementia, and Parkinson disease. It suggests these drugs may be linked to lower risk of neurodegenerative disorders, but the observational design cannot prove cause and effect or show a treatment for existing dementia.
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In this 3-year randomized clinical trial, ω-3 treatment was safe and well-tolerated but failed to reach significant reductions in WML accumulation or neuronal integrity breakdown among all participants, which may be attributable to sample size limitations.
Why it matters
Over three years, omega-3 treatment did not significantly reduce the buildup of white matter lesions or the decline in brain neuronal integrity compared with placebo. The treatment was safe and well tolerated, but it failed to reach significant reductions in these brain measures.
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The rs75932628 was associated with AD in the Greek sample.
Why it matters
In a Greek sample of 327 people with Alzheimer's and 700 healthy controls, the TREM2 R47H variant was found in three patients and no controls, a significant association. An updated meta-analysis of 27 studies linked the variant to Alzheimer's with an odds ratio of 2.98, with a similar odds ratio of 2.93 in Caucasian-only studies, while Asian studies showed no significant link. This supports R47H as a genetic risk factor in Caucasian populations.
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White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor.
Why it matters
In 50,970 older adults, this genetic study found 27 locations in the genome linked to white matter hyperintensities, the most common brain-scan sign of small vessel disease. The same risk variants were already tied to altered white matter in 1,738 young healthy adults (p = 2.5×10⁻⁷), which suggests this genetic risk acts across the lifespan. Genetic causal-inference (Mendelian randomization) analyses suggested that larger white-matter-lesion volume is linked to stroke and Alzheimer-type dementia, and higher blood pressure to larger lesion volume, even in people without diagnosed hypertension. These are genetic associations: the study points to drug targets worth testing in prevention trials but did not test any treatment.
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The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies.
Why it matters
This meta-analysis of mouse aorta studies confirms a Trem2 foamy macrophage subset among leukocytes in atherosclerosis. It concerns heart vessel disease, not Alzheimer's, and offers no Alzheimer's treatment insight.
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Increased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals.
Why it matters
In cognitively normal people, higher midlife triglycerides were linked to abnormal amyloid and tau biomarkers about 20 years later. This is an observational cohort finding, so it does not show that lowering triglycerides prevents Alzheimer disease.
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Sleep deprivation, or prolonged wakefulness, interferes with a physiological morning decrease in Aβ42.
Why it matters
In this small randomized trial of 26 healthy middle-aged men, one night of unrestricted sleep led to a 6% decrease in cerebrospinal fluid Aβ42 levels, while sleep deprivation counteracted this decrease. This suggests that sleep may affect Aβ42 levels, but the study was small and in healthy people, not patients with Alzheimer disease.
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.
- Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein
- A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease
- Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN)
- Asymmetry of post-mortem neuropathology in behavioural-variant frontotemporal dementia
- Development of a simplified smell test to identify Parkinson’s disease using multiple cohorts, machine learning and item response theory
- EEG network reorganization across Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies
- Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system
- Neuroprotective Potential of Tetraselmis chuii Compounds: Insights into Blood–Brain Barrier Permeability and Intestinal Transport
- Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: A phase 1 clinical trial
- Volatile oil of Acori tatarinowii rhizoma: potential candidate drugs for mitigating dementia