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 GGGGCC (G4C2) repeat expansion in a noncoding region of C9orf72 is the most common cause of sporadic and familial forms of amyotrophic lateral sclerosis and frontotemporal dementia.
Why it matters
In this laboratory study using fruit flies, a repeated stretch of DNA in the C9orf72 gene caused nerve damage and problems with the nuclear pore complex and RNA export. This identifies possible mechanisms and genetic modifiers for C9orf72-related ALS and frontotemporal dementia, but it is animal research and not a treatment.
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Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer's disease (AD) and other neurodegenerative diseases.
Why it matters
In AD mouse models, TREM2 deficiency eliminated TREM2+ inflammatory macrophages and reduced inflammation and amyloid and tau pathology. It is animal work and does not test a treatment or cure in patients.
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Synaptic dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and directly related to cognitive impairment.
Why it matters
Spinal fluid levels of the synaptic protein neurogranin were markedly increased in Alzheimer's dementia across three independent clinical cohorts and correlated with the rate of cognitive decline in prodromal Alzheimer's disease. The authors suggest it may be a biomarker for monitoring synaptic degeneration, but it is not a treatment, cure, or prevention.
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The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function.
Why it matters
Describes a database of gene activity, built with RNA sequencing, for eight cell types purified from mouse cerebral cortex, including neurons, glia and blood vessel cells. The authors made it available on a website as a resource for studying how the brain develops and works.
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58/100
An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis.
Why it matters
In Drosophila, expression of pure repeats but not stop codon-interrupted 'RNA-only' repeats caused adult-onset neurodegeneration, and individual poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. The findings are consistent with a dual toxicity mechanism in which both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration.
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We have identified 10 plasma proteins strongly associated with disease severity and disease progression.
Why it matters
In this study of 1,148 subjects, a panel of 10 plasma proteins predicted progression from mild cognitive impairment to Alzheimer's disease with 87% accuracy. The authors say such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints.
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58/100
Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement.
Why it matters
This laboratory work found that certain TREM2 mutations reduce the receptor's maturation, stop its shedding by ADAM proteases, and impair the phagocytic activity of cells expressing it. Lower soluble TREM2 was also seen in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia, suggesting reduced TREM2 function may contribute to increased risk for these disorders.
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MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Why it matters
Using exome sequencing, this study found mutations in the MATR3 gene in families with amyotrophic lateral sclerosis (ALS). MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a protein linked to both ALS and frontotemporal dementia, and MATR3 pathology was seen in ALS spinal cords whether or not a MATR3 mutation was present. It is genetic evidence that faulty RNA processing plays a role in motor neuron degeneration. It is not an Alzheimer's study, and it does not test any treatment or prevention.
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Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Parkinson's disease and other synucleinopathies, Alzheimer's disease (AD), and mild cognitive impairment heralding its progression to dementia.
Why it matters
This review describes that olfactory dysfunction is a common and early symptom of several neurodegenerative diseases, including Alzheimer's disease, and is related to deposition of pathological proteins such as alpha-synuclein and hyperphosphorylated tau in olfactory areas. It notes recent studies have focused on olfactory dysfunction as a potential early biomarker for diagnosis and disease progression, but reports no treatment or cure.
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CSF NfL is elevated in symptomatic FTD and correlates with disease severity.
Why it matters
In people with frontotemporal degeneration, higher cerebrospinal fluid neurofilament light chain levels tracked with disease severity and worse cognition. This marker reflects disease severity in frontotemporal degeneration and is not a treatment, cure, or prevention for Alzheimer's disease.
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Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease.
Why it matters
In 66 older people with autopsy and more than one MRI, arteriolosclerosis, myelin pallor, and higher Braak score were associated with greater white matter hyperintensity accumulation over time. The authors suggest these changes are likely driven by small-vessel disease, but this is a pathology correlation study with no treatment tested.
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Breakthrough discoveries identifying common genetic causes for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have transformed our view of these disorders.
Why it matters
This review argues that amyotrophic lateral sclerosis and frontotemporal dementia share disrupted RNA and protein homeostasis, with a possible feedforward loop including cell-to-cell prion-like spread driving progression. It is a mechanistic proposal about these two diseases, not a treatment, cure or prevention for Alzheimer's disease.
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Accumulation of β-amyloid protein (Aβ) and tau protein is the main feature of Alzheimer disease neuropathogenesis.
Why it matters
This study measured cerebrospinal fluid Aβ and tau levels before and after surgery in people given spinal anesthesia alone, spinal plus desflurane, or spinal plus isoflurane. It examined whether these anesthetics change Alzheimer-related fluid markers, not whether they treat, cure, or prevent the disease.
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Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001).
Why it matters
In cognitively normal late-middle-aged adults, APOE epsilon4 gene dose was associated with lower posterior cingulate glucose metabolism, while hippocampal volume and hippocampal glucose metabolism did not differ significantly among groups. This is an observational imaging finding and does not test treatment or prevention.
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The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes.
Why it matters
This randomized crossover study in eight healthy volunteers found that a curcuminoid/piperine extract produced no meaningful changes in the pharmacokinetics of midazolam, flurbiprofen, or paracetamol. It is a small drug-interaction study in healthy volunteers and does not test whether curcumin treats or prevents Alzheimer's disease.
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The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations.
Why it matters
This study describes the neuroimaging profile of the C9ORF72 expansion in frontotemporal dementia, finding it was more symmetrical than progranulin mutations and had less temporal lobe involvement than microtubule-associated protein tau mutations. The findings may help guide genetic testing and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network.
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The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset, sporadic Alzheimer's disease (AD).
Why it matters
In cognitively normal people, markers of amyloid build-up in the brain varied by apoE type, and in mice carrying human apoE versions, the clearance of soluble amyloid-β from the brain depended on which version was present, while amyloid production did not differ in young mice. The authors suggest APOE variants affect Alzheimer's risk by changing how amyloid-β is cleared, making clearance pathways possible targets for prevention.
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CA1 apical neuropil atrophy is apparent in patients with mild AD.
Why it matters
Using ultra-high-field 7-T MRI, this small cross-sectional study found thinning of a specific hippocampal layer in people with mild Alzheimer disease, while standard hippocampal volume did not differ from controls. It is a small imaging study of brain structure and does not test any treatment, cure, or prevention.
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We examined longitudinal associations between the apolipoprotein E ε4 allele (ApoE4(+) status) and several cognitive outcomes and tested effect modification by sex.
Why it matters
In this long-running study, carrying the apolipoprotein E ε4 allele predicted dementia, and this risk was similar in men and women. However, the link between this allele and decline in verbal memory and learning was stronger in women than in men.
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A sensitive immunohistochemical method for phosphorylated alpha-synuclein was used to stain sets of sections of spinal cord and tissue from 41 different sites in the bodies of 92 subjects, including 23 normal elderly, 7 with incidental Lewy body disease (ILBD), 17 with Parkinson's disease (PD), 9 with dementia with Lewy bodies (DLB), 19 with Alzheimer's disease with Lewy bodies (ADLB) and 17 with Alzheimer's disease with no Lewy bodies (ADNLB).
Why it matters
This tissue study found that clumps of phosphorylated alpha-synuclein are widespread in the spinal cord and peripheral organs in people with Parkinson's disease and dementia with Lewy bodies, and less so in other conditions. It describes where this pathology occurs but does not test any treatment or prevention.
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Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis.
Why it matters
In brain tissue from 15 people with sporadic, early-onset frontotemporal dementia (FTD) marked by "severe progressive behavioural and personality changes", the protein FUS stained all the abnormal clumps in nerve cells, was also found in support (glial) cells, and was present in increased insoluble form. None of the patients carried a FUS gene mutation, and the authors conclude FUS is "the pathological protein in a significant subgroup of sporadic FTD", which they put at around 10% of cases, and that FTD and ALS are "closely related conditions". This is a post-mortem study that defines an FTD subtype; it is not about Alzheimer's disease and tests no treatment or diagnostic test.
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Hyperphosphorylated tau makes up the filamentous intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease.
Why it matters
In this mouse study, brain extract from mice carrying a mutant (P301S) form of human tau was injected into the brains of mice carrying normal human tau, a strain that on its own does not form tau filaments. The study reports that the injection made the normal human tau assemble into filaments, and that the pathology spread from the injection site to neighbouring brain regions. It is animal research on how tau pathology can be transmitted and spread; it does not test a treatment and does not show that Alzheimer's spreads between people.
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58/100
To design clinical trials for the frontotemporal lobar degenerations (FTLD), knowledge about measurement of disease progression is needed to estimate power and enable the choice of optimal outcome measures.
Why it matters
This study tested how to run a one-year trial in people with frontotemporal lobar degeneration and found that two global measures showed decline in most patients, while two behavioural scales did not work well for trials. It is about designing future trials, not about treating, curing or preventing Alzheimer's disease.
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Autophagy is the principal cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress.
Why it matters
In brain tissue from people early in Alzheimer's disease, the autophagy protein beclin 1 was lower in affected regions. In mice, reducing beclin 1 lowered neuronal autophagy and caused neurodegeneration and lysosome damage. In a mouse model of Alzheimer's, reducing it also increased amyloid-beta build-up inside and outside nerve cells. The human finding is an association, and only the mouse work changed beclin 1, so this suggests autophagy is protective but tests no treatment.
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Fourteen years after transplantation into the striatum of an individual with Parkinson's disease, grafted nigral neurons were found to have Lewy body-like inclusions that stained positively for alpha-synuclein and ubiquitin and to have reduced immunostaining for dopamine transporter.
Why it matters
This study found Lewy body-like inclusions positive for alpha-synuclein and ubiquitin in grafted nigral neurons 14 years after transplantation into a person with Parkinson's disease, suggesting the disease process can affect grafted cells. It concerns Parkinson's disease and cell-based therapies, not treating, curing or preventing 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.
- METTL3-dependent RNA m6A dysregulation contributes to neurodegeneration in Alzheimer's disease through aberrant cell cycle events
- Molecular Mechanisms of Vascular Dementia: What Can Be Learned from Animal Models of Chronic Cerebral Hypoperfusion?
- Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment
- Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review
- Multi‐Targeting Makrozyklische Peptide als Nanomolare Inhibitoren der Selbst‐ und Kreuznukleation der Amyloiden Selbstassemblierung von α‐Synuclein
- Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum
- Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain
- Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia
- Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials
- Hypercapnic and Hypoxic Respiratory Response During Wakefulness and Sleep in a Streptozotocin Model of Alzheimer's Disease in Rats