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 hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with synaptic dysfunction identified as an early pathological hallmark.
Why it matters
Reviewing 72 articles on the C9orf72 gene, the most common genetic cause of ALS and frontotemporal dementia, researchers looked at synapse damage in the cerebellum. Meta-analysis showed defects in nerve-cell branches (dendrites), reduced C9orf72 in patients and neuron loss tied to toxic repeat proteins, but no overall cerebellar neuron loss. The authors conclude that lower C9orf72 protein combined with RNA foci and repeat proteins act together to damage synapses, which concerns frontotemporal dementia rather than Alzheimer's.
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These results indicate lipid droplet accumulation occurs in human DAM xMGs in AD, but is reduced in TREM2-R47H DAM xMGs, as it occurs secondary to TREM2-mediated changes in plaque proximity and reactivity.
Why it matters
Human immune cells (microglia) transplanted into Alzheimer's model mice built up fat droplets around amyloid plaques, and their gene activity resembled the fat-laden "foam cells" of clogged arteries. Cells carrying the TREM2-R47H Alzheimer's risk variant stayed further from plaques, reacted less, and built up less fat, which the authors read as the fat build-up following from the cells' response to plaques. This was done in mice, at one age, and does not test any treatment for people.
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Alzheimer's disease (AD) is the most common cause of age-related dementia.
Why it matters
This study reports that blocking microglial activation of reactive astrocytes was neuroprotective in models of Alzheimer's disease. Because it was done in models, it is early and does not establish a treatment, cure, or prevention for people.
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50/100
Widespread cortical reduction of synaptic density was documented in a cohort of DLB/PDD subjects using in vivo [11C]UCB-J PET.
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Regulation of glial activation and neuroinflammation are critical factors in the pathogenesis of Alzheimer's disease (AD).
Why it matters
YKL-40 is a widely studied spinal-fluid marker that rises with aging and early in Alzheimer's, but what it does was unknown. In a cohort of people with Alzheimer's, this study found that a *CHI3L1* gene variant that lowers spinal-fluid YKL-40 was associated with slower progression; in mice, removing the gene had no effect on astrocyte activation and modestly increased microglial activation at baseline. The human result is an association and the mouse work is early laboratory research, so it does not show that lowering YKL-40 treats or prevents Alzheimer's.
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The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovascular dysfunction in neurodegenerative diseases remain elusive.
Why it matters
In aged mouse brain endothelial cells, age-related gene expression changes involved immune signaling and the blood-brain barrier, and some of these changes overlapped with genes implicated in human Alzheimer's disease. Treatment with exenatide reversed these changes and blood-brain barrier leakage in mice, but this is animal research and does not establish a treatment for people.
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The ε4 allele of the apolipoprotein E gene (APOE ε4) is associated with an additional risk for AD.
Why it matters
In children with Down syndrome, this study found that APOE ε4 carriers showed an attentional advantage over noncarriers, while the authors note ε4 is linked to a disadvantage later in life. It is a cross-sectional study and does not test any treatment, cure, or prevention.
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Positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) reveals altered cerebral metabolism in individuals with mild cognitive impairment (MCI) and Alzheimer's dementia (AD).
Why it matters
This study developed a method using FDG-PET brain metabolic networks to predict an individual's risk of conversion from mild cognitive impairment to Alzheimer's dementia. It does not show that any treatment prevents conversion, and the work is about prediction rather than curing or preventing dementia.
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Loss of function of triggering receptor expressed on myeloid cell 2 (TREM2), a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD).
Why it matters
This study examined changes in cerebrospinal fluid soluble TREM2 across preclinical Alzheimer's disease stages in 659 cognitively normal participants. It is an observational biomarker study and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Among the most noteworthy developments in ophthalmology over the last decade has been the emergence of quantifiable high-resolution imaging modalities, which are typically non-invasive, rapid and widely available.
Why it matters
This review describes how retinal imaging may serve as a biomarker of systemic disease, noting an established association between retinal structure and Alzheimer's disease. It discusses retinal imaging for risk stratification but does not test any treatment, cure, or prevention.
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TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia.
Why it matters
In a mouse model of amyloid buildup, deleting Trem2 impaired microgliosis, raised plaque levels early but lowered them at older ages, and worsened axonal and spine damage. These are mouse findings and do not establish any treatment, cure or prevention for people.
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Until now, data on the longitudinal trajectories of amyloid accumulation, tau pathology, and brain atrophy over multiple time points remain scarce in DS.
Why it matters
This case report followed one person with Down syndrome over seven years and found that amyloid beta accumulation preceded dementia and cognitive decline, which corresponded to tau deposition in temporoparietal cortices. It is a single case report and the authors note further longitudinal studies are necessary, so it does not establish a treatment or cure.
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Studies have shown an overlap of Aβ plaques, tau tangles, and α-synuclein (α-syn) pathologies in the brains of Alzheimer's disease (AD) and Parkinson's disease (PD) with dementia (PDD) patients, with increased pathological burden correlating with severity of cognitive and motor symptoms.
Why it matters
In a mouse model, amyloid-beta plaques accelerated the seeding and spread of alpha-synuclein throughout the brain and induced hyperphosphorylated tau, with neuron loss linked to declining cognitive and motor performance. This suggests a 'feed-forward' mechanism in mice, but it is animal research and does not yet show what happens in people.
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Noncoding small RNAs, such as microRNAs, are becoming the biomarkers of choice for multiple diseases in clinical diagnostics.
Why it matters
This work introduces a CRISPR/Cas13a-powered microfluidic electrochemical biosensor for detecting microRNAs without nucleic acid amplification, achieving a limit of detection of 10 pM, and demonstrates detection of miR-19b in serum from children with brain cancer. It notes microRNA dysregulation can be associated with diseases such as dementia, but the demonstrated application is brain cancer, so it reports no treatment, cure or prevention for Alzheimer's disease.
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Astrocytes are a population of cells with distinctive morphological and functional characteristics that differ within specific areas of the brain.
Why it matters
This review proposes that loss of astrocyte function through cellular senescence could have implications for neurodegenerative disorders such as Alzheimer's disease and for the aging brain. It is a discussion of cell biology and does not report a treatment, cure or prevention.
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Identification of multiple immune-related genetic risk factors for sporadic AD (sAD) have put the immune system center stage in mechanisms underlying this disorder.
Why it matters
In human brain samples, carriers of Alzheimer's risk variants in TREM2 had fewer plaque-associated microglia and more dystrophic neurites and pathological tau than matched patients without those variants. This is observational human tissue work and does not show a treatment, cure, or prevention.
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Variants of triggering receptor expressed on myeloid cells 2 (TREM2) are associated with an increased incidence of Alzheimer's disease, as well as other neurodegenerative disorders.
Why it matters
TREM2 gene variants are linked to a higher risk of Alzheimer's disease. Using a newly built lab reporter cell, this study found that TREM2 is switched on by two fats, phosphatidylserine and phosphatidylethanolamine, which are hidden inside healthy cells and become exposed only when a cell dies. It also found hints of other, still-unidentified TREM2 triggers in mouse brain membranes. This is cell and mouse-tissue lab work: the authors say it "may suggest" how TREM2 guides the brain's immune cells, and it does not test any treatment.
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50/100
Our results demonstrate that endogenous expression of E4 by stem-cell-derived forebrain excitatory neurons predisposes neurons to calcium dysregulation and ultimately cell death.
Why it matters
In neurons grown from stem cells of Alzheimer's patients, the APOE4 form of apolipoprotein E made the cells more vulnerable to injury and caused them to release more phosphorylated tau. This is laboratory work in cells, not a treatment or cure, and it suggests a possible mechanism by which APOE4 might help tau pathology spread.
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50/100
Pathological aggregation of the transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with several neurodegenerative disorders, including ALS, frontotemporal dementia, chronic traumatic encephalopathy, and Alzheimer's disease.
Why it matters
This laboratory work found that amyloid formation by the TDP-43 low-complexity domain is controlled by electrostatic repulsion and that liquid droplets accelerate fibrillation. It is basic laboratory research, so it does not yet show any treatment, cure or prevention for Alzheimer's disease.
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TAR DNA binding protein 43 (TDP-43) is a versatile RNA/DNA binding protein involved in RNA-related metabolism.
Why it matters
This review states that TDP-43 deposits are found in the neuronal inclusions of up to 97% of sporadic ALS patients, suggesting a pivotal role in ALS pathology, and that unraveling the molecular mechanisms of TDP-43 pathology seems central to ALS therapeutics. It discusses TDP-43 mutations, mis-localization, post-translational modifications, aggregation, phase separation, and potential prion-like propagation, but reports no treatment tested in patients.
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In multiple neurodegenerative diseases, including Alzheimer's disease (AD), a prominent pathological feature is the aberrant aggregation and inclusion formation of the microtubule-associated protein tau.
Why it matters
This review examines how FTDP-17-linked MAPT mutations cause tauopathy and neurodegeneration, focusing on the prion-like properties of wild-type and mutant tau. It notes large gaps in knowledge and questions the generalizability of prion-like propagation across tauopathies, reporting no treatment, cure, or prevention.
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These results suggest a potential link between vascular risk and tau pathology in preclinical AD.
Why it matters
In 152 clinically normal older adults, elevated vascular risk and amyloid burden had a significant interactive association with subsequently measured tau in the inferior temporal cortex. This suggests that vascular risk may influence the progression of Alzheimer's pathology, but no treatment or prevention is tested.
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Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world.
Why it matters
This review describes CSF1R-related leukoencephalopathy, which typically presents with a frontotemporal dementia-like phenotype in the 40s-50s. It reports no treatment, cure, or prevention for Alzheimer's disease.
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Rare coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased risk for Alzheimer's disease (AD), but how they confer this risk remains uncertain.
Why it matters
In laboratory assays, TREM2 bound directly to forms of amyloid-beta, especially soluble oligomers, and Alzheimer's-linked TREM2 variants reduced how much amyloid-beta was taken into cells. This is laboratory work and does not show that targeting this interaction treats or prevents Alzheimer's disease.
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Better cognitive outcome and higher synaptic density in PS2APP mice was predicted by higher TSPO expression at 8 mo. The progression of TSPO activation to 13 mo also showed a moderate association with spared cognition, but amyloidosis did not correlate with the cognitive outcome, regardless of the time point.
Why it matters
In PS2APP mice, better cognitive outcome and higher synaptic density were predicted by higher TSPO expression at 8 months, and progression of TSPO activation to 13 months showed a moderate association with spared cognition, while amyloidosis did not correlate with cognitive outcome at any time point. This animal PET study indicates that a continuing microglial response seems to impart preserved cognitive performance, but it does not establish a treatment, cure, or prevention for human Alzheimer's disease.
From across this topic
9 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 9. The same 9 appear here every time.
- The Impact of Immunotherapy Drugs on the Human Nervous System
- Quantitative proteomics characterization of a mouse embryonic stem cell model of Down syndrome
- Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice
- Plasma lipidome dysregulation in frontotemporal dementia reveals shared, genotype‐specific, and severity‐linked alterations
- Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders
- TREM2-induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology
- Helicobacter pylori filtrate induces Alzheimer-like tau hyperphosphorylation by activating glycogen synthase kinase-3β
- Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis
- Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease