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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A study with a more intensive multidomain intervention might bring further insights on this topic.
Why it matters
In this secondary analysis of 1,679 older adults with memory complaints, no association was found between a lifestyle multidomain intervention, omega-3 supplementation, or both, and the onset of clinically meaningful depressive symptoms. There was only a trend toward reduced risk of severe depressive symptoms in the combined group, which was not statistically significant.
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A possible involvement of the gene IL1RAP (interleukin-1 receptor-associated protein) in the pathogenesis of Alzheimer's disease (AD) has been suggested in GWASs of cerebrospinal fluid (CSF) tau levels and longitudinal change in brain amyloid burden.
Why it matters
This study examined whether genetic variations near the IL1RAP gene are related to Alzheimer's disease risk, spinal fluid tau and amyloid biomarkers, and cognitive decline. It is a genetic association study and does not test any treatment or cure.
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Frontotemporal lobar degeneration causes a spectrum of complex degenerative disorders including frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome, each of which is associated with changes in the principal neurotransmitter systems.
Why it matters
This review proposes that changes in neurotransmitter systems including dopamine, noradrenaline, serotonin, acetylcholine, glutamate, and gamma-aminobutyric acid contribute to symptoms of frontotemporal lobar degeneration beyond neuronal loss and atrophy. It argues that targeting these selective deficiencies is an important strategy to reduce disease burden and improve quality of life, while disease-modifying therapies aiming to slow neuropathological progression are developed.
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56/100
Amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) constitutes a devastating disease spectrum characterized by 43-kDa TAR DNA-binding protein (TDP-43) pathology.
Why it matters
This study created a TDP-43 knock-in mouse with a human-equivalent mutation and found cognitive dysfunction, loss of parvalbumin interneurons and perturbed autoregulation. It is animal research, so it does not establish a treatment or cure for people.
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Alzheimer's disease (AD) is a neurodegenerative disease that causes late-onset dementia.
Why it matters
This mouse study used humanized TREM2 mice to look at the R47H variant, which the record says "triples AD risk in genome-wide association studies". Earlier lab work had shown that R47H impairs TREM2's binding to anionic lipids, but its effect in living animals was unknown. The title reports "microglia-intrinsic and -extrinsic effects of R47H", but alzhub's record does not include the results, so read the original paper for what those effects are. This is animal research and does not test any treatment in people.
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PERSI showed superior test-retest reproducibility (1.84%) and group separation ability (cross-sectional Cohen d = 9.45; longitudinal Cohen d = 2.34) compared with other reference regions.
Why it matters
This study describes a new method, PERSI, for quantifying flortaucipir F 18 tau PET scans, which showed better test-retest reproducibility and group separation than other reference regions. The authors suggest this could improve disease staging and measurement of tau changes over time for evaluating potential therapies, but no treatment itself was tested.
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Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a progressive degenerative white matter disorder.
Why it matters
This article combines two illustrative patient cases with a systematic review of ALSP, a progressive white matter brain disorder linked to mutations in the CSF1R gene, which regulates cells including microglia. Because ALSP has been mistaken in life for conditions including Alzheimer disease and frontotemporal dementia, the authors suggest it may be significantly underdiagnosed and recommend consistently using the single term ALSP.
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Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD).
Why it matters
Researchers bred mice that develop human tau pathology (the PS19 line) to have either normal Trem2 or no Trem2 at all, because TREM2's role "in the context of tau pathology has not yet been characterized." The paper's title reports that losing TREM2 "attenuates neuroinflammation and protects against neurodegeneration" in these mice, the reverse of earlier amyloid studies, where TREM2 was "protective". This is a gene-knockout experiment in mice, not a treatment, and our stored record does not include the detailed results.
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Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration.
Why it matters
In mice and brain slice experiments, loss of TREM2 reduced how well microglia moved toward injured neurons and toward sites of damage. This is animal and laboratory work on a risk gene, not a treatment or prevention study in people.
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Neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTD), Lewy body disease (LBD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have in common that protein aggregates represent pathological hallmark lesions.
Why it matters
This review concludes that amyloid beta, tau, alpha-synuclein, and TDP-43 pathologies can co-exist and interact at the molecular level, with additive effects on brain damage. It hypothesizes a cascade of events in neurodegenerative disease development but reports no treatment, cure, or prevention.
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In this study, altered AQP4 expression was associated with aging brains.
Why it matters
In brain tissue from deceased people, loss of the water-channel protein aquaporin-4 from around blood vessels was linked to having Alzheimer's disease and to more amyloid plaques and tau tangles. This kind of post-mortem association study cannot show whether the change causes the disease or is a result of it, so it does not yet point to a treatment.
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Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Why it matters
Two mouse lines lacking C9orf72 developed normally without motor neuron disease but showed enlarged spleen and lymph nodes, lysosomal buildup in macrophages and microglia, and age-related neuroinflammation. This suggests that loss of C9orf72 function in immune cells may contribute to disease, but it is mouse work and not a treatment.
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Stress granules are membrane-less organelles composed of RNA-binding proteins (RBPs) and RNA.
Why it matters
This laboratory work suggests that liquid-liquid phase separation of certain proteins helps build stress granules and may link persistent stress granules to fibrillar protein pathology in diseases such as amyotrophic lateral sclerosis and frontotemporal dementia. It is early, mechanism-focused research and does not test any treatment, cure or prevention for Alzheimer's disease.
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56/100
Loss-of-function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known.
Why it matters
In 1,369 people with Parkinson's disease, GBA mutations and the E326K polymorphism were linked to a distinct pattern of cognitive deficits. This is a genetic association study and does not show any treatment, cure or prevention for Alzheimer's disease.
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Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord.
Why it matters
This review describes cortical superficial siderosis as a key feature of cerebral amyloid angiopathy, a small vessel disorder that can lead to bleeding in the brain and dementia, and notes preliminary data suggesting a link to future bleeding risk. It is about a blood vessel condition and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer's disease (AD) because of important differences in patient management and outcome.
Why it matters
This multicenter study tested whether heart imaging with 123I-MIBG could distinguish dementia with Lewy bodies from Alzheimer's disease, based on cardiac sympathetic degeneration occurring in DLB but not AD. The provided text does not report the accuracy results, so it is unknown how well this imaging test performs for diagnosis.
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56/100
The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE ε4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p ≤ 0.005).
Why it matters
Among people with mild cognitive impairment, those with suspected non-amyloid pathology (SNAP) had a higher risk of progressive cognitive decline than those with neither amyloid nor neurodegeneration markers. The SNAP group had more severe hippocampal atrophy than the group with both amyloid and neurodegeneration, and a different proportion of APOE ε4 carriers.
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Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline.
Why it matters
This study used a statistical model to examine whether reduced brain glucose metabolism (measured by FDG PET) links cerebrospinal fluid Alzheimer biomarkers to changes in cognitive function. It is an observational cohort study, so it cannot show that any treatment targeting these markers would change cognition.
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We confirm only p.R47H as a risk factor for AD (odds ratio or OR = 2.19; 95% confidence interval or CI = 1.04-4.51; P = .03). p.R47H does not significantly alter risk for frontotemporal dementia (OR = 0.81), variant or sporadic CJD (OR = 1.06 95%CI = 0.66-1.69) in our cohorts.
Why it matters
Across large patient groups, only the p.R47H TREM2 variant was confirmed as a risk factor for Alzheimer's disease, and it did not significantly alter risk for frontotemporal dementia or Creutzfeldt-Jakob disease. This is a risk-factor finding and does not provide a treatment, cure, or prevention.
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Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA).
Why it matters
In this 24-week trial of 21 patients with mixed dementia, galantamine improved quality of life and cognitive performance, but adding nimodipine provided no advantage over galantamine alone. The authors state the small sample size precludes any definitive conclusions.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which microglia play a significant and active role.
Why it matters
This study genotyped DNA from 923 people with sporadic ALS (a fatal motor neuron disease, different from Alzheimer's) and 1,854 healthy controls, all self-reported non-Hispanic white and recruited at US ALS clinics. It asked whether the rare TREM2 variant p.R47H, which earlier studies had linked to Alzheimer's risk, is also a risk factor for ALS, and whether TREM2 expression is altered in the disease. The summary held here stops before the results, so this page cannot say what the study found, and it does not test any treatment, cure or prevention for Alzheimer's disease.
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Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are devastating neurodegenerative disorders with clinical, genetic, and neuropathological overlap.
Why it matters
This study found that the antisense strand of the expanded C9ORF72 repeat forms RNA clumps and produces three proteins in cells and in brain tissue from people with c9FTD/ALS. It identifies possible disease mechanisms but does not test a therapy or show benefit in patients.
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α-Synuclein is the major component of filamentous inclusions that constitute the defining characteristic of neurodegenerative α-synucleinopathies.
Why it matters
In normal mice, injecting clumped (fibril) alpha-synuclein — taken from the brains of people with dementia with Lewy bodies, or made in the lab — set off Lewy-body-like changes, while injecting the non-clumped (soluble) form did not. The injected human protein was gone in about a week, yet the mice's own alpha-synuclein began building up about 3 months later, which the authors read as evidence the clumps act in a "prion-like" way. It gives researchers a mouse model for studying how this disease progresses and for testing future treatments; it is animal research, tested no treatment, and does not show the disease passes between people.
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Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72.
Why it matters
This review discusses how the C9orf72 repeat expansion and shared TDP-43 pathology link ALS and frontotemporal dementia, and how genetic heterogeneity challenges the idea of ALS as one disease. It is a discussion of disease concepts and does not report a treatment or cure.
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Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression.
Why it matters
This study assessed amyloid precursor protein metabolites in the CSF of patients with bipolar disorder, drawing on biomarkers previously used to study neurodegeneration in Alzheimer's disease. It concerns bipolar disorder and does not test any treatment, cure, or prevention for Alzheimer's 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.
- Serotonin in Parkinson's disease
- The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease
- Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System
- Sex differences for clinical presentations and co-pathologies in four-repeat tauopathies
- Inflammation is detrimental for neurogenesis in adult brain
- TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia
- TNF-alpha inhibition as a treatment strategy for neurodegenerative disorders: new drug candidates and targets
- Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction
- Astrocytes upregulate interleukin-15 in response to neuroinflammation during Alzheimer's disease
- Functionalization of Brain Region-specific Spheroids with Isogenic Microglia-like Cells