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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The human genome contains over one million short tandem repeats.
Why it matters
This review describes four major ways that expanded short tandem repeats cause disease, including in ALS and frontotemporal dementia, and suggests that these mechanisms may offer therapeutic targets. It does not test any treatment or prevention for Alzheimer's disease, so it has no direct implications for treating, curing, or preventing the disease.
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Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9).
Why it matters
This study shows that TREM2 recognises mycobacterial cell-wall mycolic acid-containing lipids and suggests a mechanism by which mycobacteria control host immunity via TREM2. It concerns mycobacterial infection, not Alzheimer's disease, and reports no treatment, cure, or prevention for Alzheimer's disease.
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Tau IQ successfully calculated global tau load (Tau L ) in all 791 scans analyzed (range, -3.5% to 185.2%; mean ± SD, 23% ± 20.5%) with a nonzero additional local tau component being required in 31% of all scans (cognitively normal [CN], 22%; mild cognitive impairment [MCI], 35%; dementia, 72%).
Why it matters
This paper describes a new image-based method, Tau IQ, for measuring tau load on tau PET scans, which performed better than an existing approach in longitudinal analyses. It is a tool for quantifying scans and is proposed as useful for clinical trials testing treatments that aim to reduce tau deposition.
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As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature.
Why it matters
This laboratory study found that the SARS-CoV-2 spike protein caused significant changes in in-vitro models of the human blood-brain barrier, and that ACE2 expression was upregulated in cases of hypertension and dementia. These are early cell-culture findings about the virus and the blood-brain barrier, not a treatment, cure or prevention for Alzheimer's disease.
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Compared to controls, mean CSF NPTX2 levels were lower in DS at all AD stages; aDS (0.6-fold, adj.p 0.07).
Why it matters
This study found that cerebrospinal fluid levels of NPTX2 are lower in adults with Down syndrome at all stages of Alzheimer disease compared to controls. It supports NPTX2 as a potential biomarker, but it does not test any treatment or cure.
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Cell function and activity are regulated through integration of signaling, epigenetic, transcriptional, and metabolic pathways.
Why it matters
This study is about a new lab technology for measuring RNA and protein activity in single cells and about immune cells in tumors, not about Alzheimer's disease. It provides no direct information on treating, curing or preventing Alzheimer's.
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A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene.
Why it matters
In brain organoids grown from hair samples of people with Down syndrome, Alzheimer-like amyloid and tau changes appeared for 71% of donors, and whether a donor's organoids showed them was consistent across repeat experiments. In organoids that had no such changes, removing the extra copy of the BACE2 gene caused them to appear, and the authors report a matching pattern of amyloid fragments in the spinal fluid of people with Down syndrome. They propose that the extra BACE2 copy acts as a brake on Alzheimer pathology that may help explain why about 30% of people with Down syndrome have delayed dementia. This is lab-dish work, not a test or a treatment.
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Neuroinflammation is an important host defense response to secondary brain injury after intracerebral hemorrhage (ICH).
Why it matters
This study tested TREM2 activation in a mouse model of intracerebral hemorrhage, not Alzheimer's disease. It provides no evidence about treating, curing, or preventing Alzheimer's disease.
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ATP13A2 (PARK9) is a late endolysosomal transporter that is genetically implicated in a spectrum of neurodegenerative disorders, including Kufor-Rakeb syndrome-a parkinsonism with dementia 1 -and early-onset Parkinson's disease 2 .
Why it matters
This study found that the ATP13A2 protein acts as a lysosomal exporter of polyamines, especially spermine, and that disease-linked mutants of this protein work poorly. The work concerns Parkinson's disease and related disorders, not Alzheimer's disease, and does not test any treatment, cure, or prevention for Alzheimer's.
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Loss-of-function (LOF) variants of TREM2, an immune receptor expressed in microglia, increase Alzheimer's disease risk.
Why it matters
Variants that weaken TREM2, an immune receptor on the brain's microglia, are linked to higher Alzheimer's risk, and this laboratory study asked how TREM2 affects the way these cells handle fats. In long-running myelin-damage experiments, microglia lacking TREM2 still ate myelin debris but could not clear its cholesterol, which built up as cholesteryl ester; they also stayed in a resting ("largely homeostatic") state instead of switching to a disease-response state, which the authors link to nerve-cell damage. A similar cholesteryl-ester build-up was seen in glial cells lacking APOE; this is cell-biology research, not a test of any Alzheimer's treatment.
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Microglial activation participates in white matter injury after cerebral hypoperfusion.
Why it matters
In rats with reduced brain blood flow, this study explored whether activated microglia worsen white matter injury through the complement C3-C3aR pathway. Because the work was done in animals, it does not yet show whether blocking this pathway would help people with Alzheimer's disease.
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CSF synaptic biomarkers, particularly NPTX2, which regulates synaptic homeostasis, relate to cognition and predict progression in AD beyond Aβ1-42 and Tau.
Why it matters
This study found that certain synaptic proteins measured in cerebrospinal fluid, especially NPTX2, tracked with cognition and predicted decline over 2-3 years in people with mild cognitive impairment and Alzheimer's, beyond amyloid and tau. These markers may be useful for prognosis and clinical trials, but they are measurements, not a treatment.
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Early identification of dementia at the stage of mild cognitive impairment (MCI) is crucial for timely diagnosis and intervention of Alzheimer's disease (AD).
Why it matters
This paper proposes a computer method for analyzing functional MRI to help diagnose Alzheimer's disease at the mild cognitive impairment stage. It is a diagnostic technique and does not provide a treatment, cure, or prevention.
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The tau protein aggregates in aging and Alzheimer disease and may lead to memory loss through disruption of medial temporal lobe (MTL)-dependent memory systems.
Why it matters
This imaging study found that greater tau burden in anterior-temporal regions was associated with higher local coherence in the hippocampus and disconnection from other medial temporal lobe memory regions, and that higher hippocampal local coherence predicted worse memory performance. It describes a possible mechanism of memory decline and does not test any treatment, cure or prevention.
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Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD).
Why it matters
In 385 elderly subjects followed for a mean of 4 years, higher cerebrospinal fluid soluble TREM2 at baseline was associated with slower memory and cognitive decline in those positive for amyloid and tau markers, and a higher sTREM2-to-p-tau181 ratio predicted slower progression to dementia. This suggests sTREM2 could be a marker of slower decline, but it does not show that raising it treats or cures Alzheimer's disease.
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Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) TREM2 protein levels are different between AD cases and controls.
Why it matters
This study analyzed TREM2 brain transcript-specific expression and alternative splicing in Alzheimer's disease cases, TREM2 mutation carriers and cognitively normal controls. It is a genetic and expression study and does not show that targeting TREM2 treats, cures or prevents Alzheimer's disease.
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The correlation between white and gray matter disappeared after partial-volume correction in 11 C-PIB ( r 2 = 0) but persisted for 18 F-flortaucipir ( r 2 = 0.27), demonstrating that the correlation between white and gray matter signal in 18 F-flortaucipir is not solely due to partial-volume effects.
Why it matters
This analysis found that off-target signal from the putamen and thalamus explained much of the variability in cortical flortaucipir signal in amyloid-negative healthy controls, and that this variability correlated with white matter signal and age-related off-target signal. The authors note this noise could pose challenges when studying early tau accumulation.
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Current models of progression in neurodegenerative diseases use neuroimaging measures that are averaged across pre-defined regions of interest (ROIs).
Why it matters
This is a computer modeling study that proposes a new way to map how brain shrinkage spreads over time in neurodegenerative diseases like Alzheimer's. It is a technical tool for research and does not test any treatment, cure, or prevention in patients.
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TDP-43 proteinopathy is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia where cytoplasmic TDP-43 inclusions are observed within degenerating regions of patient postmortem tissue.
Why it matters
Using an optogenetic cell model, this study found that TDP-43 inclusions form through interactions between low-complexity domains that RNA binding can oppose, and that oligonucleotides matching TDP-43 target sequences prevented inclusions and rescued toxicity. These are laboratory findings and not yet a treatment for patients.
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TREM2 was suggested to be an important regulator of microglia during neurodegeneration, but previous studies report conflicting results in relation to soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF) when using clinical criteria to classify Alzheimer's disease (AD).
Why it matters
In 497 people from a prospective Alzheimer's cohort grouped by spinal-fluid biomarkers, levels of soluble TREM2 (a sign of brain immune activity) were associated with markers of nerve-cell damage and tau, but not with amyloid. Levels rose over time in people with abnormal tau, but were not related to changes in thinking and memory over time. The authors see it as a possible complementary marker of neuroinflammation; this observational study does not show it can diagnose, treat or prevent Alzheimer's.
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Alzheimer's disease (AD), the most common form of dementia, is characterized by the abnormal accumulation of amyloid plaques and hyperphosphorylated tau aggregates, as well as microgliosis.
Why it matters
This study examined the effects of partial and complete loss of TREM2 on microglial function and tau-related deficits, testing the idea that risk variants act through loss of function. It is experimental work and does not establish a treatment, cure or prevention for Alzheimer's.
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Traumatic brain injury has been associated with increased risk of Parkinson disease and parkinsonism, and parkinsonism and Lewy body disease (LBD) can occur with chronic traumatic encephalopathy (CTE).
Why it matters
Among deceased contact sports athletes, those with both chronic traumatic encephalopathy and Lewy body disease were more likely to have amyloid deposition, dementia and parkinsonism. This is an autopsy comparison and does not test treatment or prevention.
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Predicting the progression of cognitive decline in Alzheimer's disease (AD) is important for treatment selection and patient counseling.
Why it matters
In 124 patients with Alzheimer's dementia taking cholinesterase inhibitors, the size of the basal forebrain (but not the hippocampus) predicted later decline in overall thinking. This suggests a brain scan measure might help predict how someone will do on this type of treatment, but it does not show that the treatment itself changes the disease course.
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In amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), cytoplasmic aggregates of hyperphosphorylated TDP-43 accumulate and colocalize with some stress granule components, but how pathological TDP-43 aggregation is nucleated remains unknown.
Why it matters
In fruit flies, turning down the enzyme tankyrase reduced TDP-43, a protein that clumps in ALS and frontotemporal dementia, building up outside the cell nucleus and "potently mitigates neurodegeneration". In lab and cell experiments, the molecule tankyrase makes (poly(ADP-ribose)) drew TDP-43 into stress granules, which "initially protects" it, but under long-term stress those granules resolve, "leaving behind aggregates of phosphorylated TDP-43". A tankyrase-blocking compound reduced TDP-43 clumps in mammalian cells; the authors say this "could have therapeutic utility for ALS and FTD", but it was not tested in people and the study does not address Alzheimer's.
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Alzheimer's disease is a genetically complex disorder; rare variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been shown to as much as triple an individual's risk of developing Alzheimer's disease.
Why it matters
This review explains that rare TREM2 variants can as much as triple Alzheimer's risk and cause partial loss of TREM2 function, altering microglial behavior including their response to amyloid plaques. It supports immune and inflammatory pathways being involved in causing the disease, but reports no treatment.
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.
- The genetic epidemiology of neurodegenerative disease
- Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy
- SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid β protein oligomerization and memory loss in mouse model of Alzheimer disease
- Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation
- Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau
- TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update
- Abnormal behaviors and glial responses in an animal model of tau pathology
- Induction of serine racemase expression and D-serine release from microglia by amyloid beta-peptide
- Isoflurane-induced apoptosis: a potential pathogenic link between delirium and dementia
- Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells