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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There is accumulating evidence that synaptic loss precedes neuronal loss and correlates best with impaired memory formation in Alzheimer's disease (AD).
Why it matters
This study tested cerebrospinal fluid SNAP-25 and the SNAP-25/Aβ42 ratio as markers for predicting cognitive decline and brain structural change in ADNI. It evaluates diagnostic markers, so it does not provide a treatment, cure or prevention.
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Microglia are activated after neuronal injury and in neurodegenerative diseases, and trigger neuroinflammation in the central nervous system (CNS).
Why it matters
This review explains that microglia-driven inflammation can be both helpful and harmful to neurons, and that timing and amount of microglial activation may decide whether neurons survive. It argues that understanding how microglia are activated is needed before microglia-targeted therapies can be developed.
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Although exact causes of Parkinson disease (PD) remain enigmatic, mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuron susceptibility in both familial and sporadic PD.
Why it matters
Levels of a marker of mitochondrial cleanup (p-S65-Ub) increased with age and disease in brain samples from normal aging and Lewy body disease cases. The authors suggest this marker could be useful, but the study does not test any treatment, cure, or prevention for Alzheimer's disease.
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hnRNPA2, a component of RNA-processing membraneless organelles, forms inclusions when mutated in a syndrome characterized by the degeneration of neurons (bearing features of amyotrophic lateral sclerosis [ALS] and frontotemporal dementia), muscle, and bone.
Why it matters
This laboratory work describes how the hnRNPA2 protein's low-complexity domain assembles and aggregates, and how disease-causing mutations and arginine methylation change these assemblies. It is basic mechanistic research and does not test any treatment, prevention or cure in people.
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Alzheimer's disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles.
Why it matters
This study compared cortical gene expression between Alzheimer's disease patient brains and mouse models, finding that commonly altered genes correlated with inflammatory response or immunological disease. It links amyloidosis and neuroinflammation but reports no treatment, cure or prevention for Alzheimer's disease.
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See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article.
Why it matters
In a transgenic rat model of Alzheimer's disease, hyperphosphorylated tau appeared in the locus coeruleus before the entorhinal cortex or hippocampus, and the rats had impaired reversal learning that was restored by chemogenetic activation of the locus coeruleus. These findings are in animals and point to locus coeruleus-based approaches as a possible direction for therapy.
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We have characterised the proteolytic cleavage events responsible for the shedding of triggering receptor expressed on myeloid cells 2 (TREM2) from primary cultures of human macrophages, murine microglia and TREM2-expressing human embryonic kidney (HEK293) cells.
Why it matters
In lab-grown human immune cells, mouse brain immune cells (microglia) and engineered kidney cells, the TREM2 protein was steadily cut at one spot, between amino acids 157 and 158, releasing a fragment into the surrounding fluid; blocking the enzyme ADAM10 stopped this, while blocking ADAM17 did not. The Alzheimer's-linked H157Y variant, which changes that exact spot, was shed faster in kidney cells, and the authors suggest this extra shedding may come from a different, unidentified enzyme rather than ADAM10. This is cell work only: it did not test whether faster shedding affects Alzheimer's risk, and it does not show that blocking shedding treats or prevents the disease.
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50/100
Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders, including Alzheimer's disease.
Why it matters
In double-transgenic mice overexpressing mutant human tau crossed with mice carrying a noncleavable p35 mutant, significant reduction of phosphorylated tau and its seeding activity was observed. This is an animal and iPSC model study of frontotemporal dementia, so it does not establish a treatment or cure for Alzheimer's disease in people.
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Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.
Why it matters
In this postmortem study, the amount of fibrinogen labeling in subcortical white matter was not significantly linked to white matter abnormalities seen on MRI or under the microscope. Among people with normal MRI, more fibrinogen was linked to a lower risk of clinical dementia, but the study could not show a role for blood-brain barrier dysfunction in causing white matter damage.
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Molecular subtypes of sporadic CJD show different levels of plasma tau.
Why it matters
In this autopsy-based cohort, plasma tau and neurofilament light were strongly increased in Creutzfeldt-Jakob disease and showed similar diagnostic performance to the corresponding cerebrospinal fluid measures. The authors state these markers are not disease-specific and support their use to identify or rule out neurodegeneration, not to treat, cure or prevent Alzheimer's disease.
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Approximately 70 human RNA-binding proteins (RBPs) contain a prion-like domain (PrLD).
Why it matters
About 70 human RNA-binding proteins carry a "prion-like domain" that helps them form liquid droplets inside cells as part of normal function. This review argues that the same property "appears to render" proteins such as TDP-43 and FUS prone to clumping, and these proteins have been linked through pathology and genetics to ALS, frontotemporal dementia and multisystem proteinopathy. It summarises earlier work and proposes, without testing, that disaggregase proteins such as Hsp104 could be a future treatment strategy. It does not study Alzheimer's disease or patients.
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Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease.
Why it matters
This review argues that age-related vascular and microcirculatory dysfunction contributes to dementia including Alzheimer's disease, and that targeting these mechanisms may help preserve brain health. It reports no tested treatment, cure or prevention in patients.
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Cytoplasmic TDP-43 aggregation is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
Why it matters
This study found that exosomes may help spread pathological TDP-43, but that blocking exosome production worsened disease in mice, suggesting that inhibiting exosomes would not be a good therapeutic strategy. It is an animal and cell study and 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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ApoE on high-density lipoproteins is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS).
Why it matters
This review describes how the apoE4 protein has altered cholesterol handling in the brain compared with apoE2 and apoE3, and is associated with Alzheimer's disease. It suggests that small molecules called structure correctors, which block a structural feature of apoE4, could potentially prevent apoE4-related damage, though this is not yet a treatment.
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The aggregation of Aβ42-peptides and the formation of drusen in age-related macular degeneration (AMD) are due in part to the inability of homeostatic phagocytic mechanisms to clear self-aggregating Aβ42-peptides from the extracellular space.
Why it matters
In age-related macular degeneration retina and stressed microglial cells, TREM2 was reduced, and a microRNA appeared to down-regulate it. This concerns macular degeneration, not Alzheimer's disease treatment or prevention.
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Microglia-mediated proteolysis of the triggering receptor expressed on myeloid cells-2 (TREM-2) produces soluble TREM-2 (sTREM-2) that can be measured in cerebrospinal fluid (CSF) samples.
Why it matters
This study investigated soluble TREM-2 in cerebrospinal fluid as a potential biomarker for multiple sclerosis and to follow treatment effects. It concerns multiple sclerosis, not Alzheimer's disease, and does not report any treatment, cure, or prevention for Alzheimer's disease.
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Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness.
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The triggering receptor expressed on myeloid cells 2 (TREM2) is an Ig-like V-type receptor expressed by populations of myeloid cells in the central nervous system and periphery.
Why it matters
In laboratory tests, the immune-cell receptor TREM2 bound apolipoprotein E (ApoE), pulling it out of spinal fluid and blood serum and binding purified ApoE. The Alzheimer-linked TREM2 variant R47H, and other mutations at the same spot, "markedly reduced" that binding, though the summary gives no figures. The authors say this links two Alzheimer's risk factors and "may provide important clues" to disease, but no people, animals or treatments were studied.
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Myeloid-lineage cells accomplish a myriad of homeostatic tasks including the recognition of pathogens, regulation of the inflammatory milieu, and mediation of tissue repair and regeneration.
Why it matters
This review states that mutations in TREM2 increase the risk for Alzheimer's disease and other neurodegenerative disorders and discusses TREM2 and DAP12 signaling. It reports no treatment, cure or prevention for Alzheimer's disease.
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Therapeutic options for patients with amyotrophic lateral sclerosis (ALS) are currently limited.
Why it matters
This paper describes how TDP-43 protein clumps are a shared feature of almost all ALS and tau-negative frontotemporal dementia cases, and proposes this as a target for designing new treatments. It concerns ALS and frontotemporal dementia, not Alzheimer's disease, and reports no treatment, cure, or prevention for Alzheimer's.
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Cognitive impairment is highly prevalent among individuals with late-life depression (LLD) and tends to persist even after successful treatment.
Why it matters
In 80 older adults with remitted depression, those with mild cognitive impairment had different levels of 24 blood proteins and more white matter hyperintensities, but no difference in brain amyloid. It is about biological markers in late-life depression and does not test any treatment, cure or prevention.
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Elevated CSF τ is considered a biomarker of neuronal injury in newly developed Alzheimer's disease (AD) and mild cognitive impairment (MCI) criteria.
Why it matters
This study compared cerebrospinal fluid tau protein levels in people with Alzheimer's disease, progressive supranuclear palsy and normal controls. It is a biomarker comparison study and does not test any treatment, cure or prevention for Alzheimer's disease.
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Alzheimer disease (AD) is a growing problem for aging populations worldwide.
Why it matters
This review links disrupted glucose metabolism and the O-GlcNAc process to Alzheimer's disease and notes that no treatments currently stop or slow it. It discusses possible targets for future therapy but reports no tested treatment or cure.
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Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS).
Why it matters
In postmortem tissue from 28 donors, alpha-synuclein aggregates were found in the peripheral autonomic nervous system of all Lewy body disease cases, and the authors suggest this may help early diagnosis of Parkinson's disease. It is a pathology study about diagnosis, not about treating, curing, or preventing Alzheimer's disease.
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Neuroinflammation is central to the common pathology of several acute and chronic brain diseases.
Why it matters
This review argues that excessive and prolonged neuroinflammation causes and accelerates long-term neurodegenerative disease, including dementia. It is a review of mechanisms and reports no treatment, cure or prevention.
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.
- Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial
- APOE ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies
- Study of spindle microtubule reassembly in cells from Alzheimer and Down syndrome patients following exposure to colcemid
- The role of Tau, amyloid-β and neuroinflammation in the association between cognition and white matter hyperintensities in a southeast Asian cohort
- The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia
- Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain
- TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis
- Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line
- Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging
- Differential effects of mitochondrial heat shock protein 60 and related molecular chaperones to prevent intracellular beta-amyloid-induced inhibition of complex IV and limit apoptosis