Each study has a usefulness score out of 100 (rubric version 4.0). Tap a score to see what makes it up.
Download bibliography of all 4,766 studies, highest score first: BibTeX (.bib) · RIS (.ris)
Highest usefulness score first. Studies without a score come last.
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Transactivation response DNA-binding protein 43 (TDP-43) is a principal component of ubiquitinated inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis (ALS).
Why it matters
In transgenic mice, expressing wild-type human TDP-43 caused TDP-43 phosphorylation, mitochondrial aggregation, motor deficits and early mortality. This is an animal model of disease mechanisms, not evidence that any treatment helps patients.
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Mutations in fused in sarcoma (FUS) are a cause of familial amyotrophic lateral sclerosis (fALS).
Why it matters
This laboratory study found that many ALS-associated mutations in the FUS protein disrupt its normal transport into the nucleus, leading to clumps in the cytoplasm. It proposes that nuclear import defects and cellular stress are involved in FUS-related diseases, but this is mechanistic research and not a treatment.
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Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are usually associated with loss of dopaminergic neurons.
Why it matters
This review argues that in Parkinson's disease and dementia with Lewy bodies, alpha-synuclein aggregates are mostly at presynapses and that synaptic dysfunction rather than cell death may cause symptoms. It raises the possibility that these diseases may eventually be treatable but reports no treatment tested in patients.
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53/100
Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype.
Why it matters
In 37 frontotemporal lobar degeneration cases that were negative for tau and TDP-43, 34 (92%) had FUS protein pathology, marking FTLD-FUS as an important subtype. The aFTLD-U form studied here appeared as behavioural-variant frontotemporal dementia with a mean onset age of 41, frequent psychotic symptoms (36%) and rare motor symptoms (3%), and no FUS gene mutations were found. This is a frontotemporal dementia study, not an Alzheimer's study, and it reports no treatment or prevention.
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Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of beta-amyloid (Abeta) plaques and tau-laden neurofibrillary tangles.
Why it matters
Mice with amyloid, tau and alpha-synuclein pathology together showed faster cognitive decline and more accumulation of all three proteins than mice with alpha-synuclein alone. This is animal work suggesting these proteins interact to worsen disease, but it does not test a treatment in people.
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53/100
Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE).
Why it matters
This review of 48 published, brain-tissue-confirmed cases, plus detailed findings in 3 professional athletes (a football player and 2 boxers), describes chronic traumatic encephalopathy (CTE) after repetitive head injury: memory, behaviour and personality changes, parkinsonism, and speech and gait problems. The authors report a tau pattern they say sets CTE apart from other tauopathies, concentrated in the superficial cortex, the depths of brain folds and around blood vessels, with beta-amyloid deposits in fewer than half the cases. It describes cases only, so it cannot show how common CTE is in athletes, and it does not test any treatment or prevention.
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Non-amyloid, ubiquitinated cytoplasmic inclusions containing TDP-43 and its C-terminal fragments are pathological hallmarks of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder, and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U).
Why it matters
This laboratory study found that the TDP-43 protein clumps on its own and that ALS-linked mutations in a specific part of the protein increase clumping and toxicity. This helps explain how TDP-43 may cause disease but does not test a treatment or cure.
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Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain.
Why it matters
In an elderly population sample, this study found tau pathology in the hippocampus was common and spread in a hierarchical pattern that was linked to dementia. It helps understand how tau pathology progresses and may aid clinical assessment, but it does not test a treatment or cure.
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Therapeutic preservation of neuronal PGC-1alpha expression promotes the nonamyloidogenic processing of amyloid precursor protein precluding the generation of amyloidogenic Abeta peptides.
Why it matters
In donated brain tissue (hippocampus) from people with and without Alzheimer's, levels of PGC-1alpha — a protein that switches on other genes — were lower the more advanced the person's dementia had been, and lower levels went with more amyloid plaque and amyloid-beta 42. In mouse nerve cells grown in a dish under high sugar, putting PGC-1alpha back reduced amyloid production, which led the authors to suggest protecting PGC-1alpha as a treatment idea. This is a postmortem link plus a lab-dish experiment; it has not been shown to treat or prevent Alzheimer's in people.
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Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques.
Why it matters
In 14 people with mild cognitive impairment, half showed increased amyloid retention on PET, and microglial activation was measured as a possible therapeutic target. This was a small imaging study, so it does not show that targeting microglia actually treats or prevents Alzheimer's disease.
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The MRI and 1H MRS findings in single-domain aMCI are consistent with a pattern similar to that of Alzheimer disease.
Why it matters
This case-control study found that people with single-domain amnestic mild cognitive impairment tended to have small hippocampal volumes and elevated myo-inositol to creatine ratios. It describes imaging and spectroscopy patterns that may help distinguish mild cognitive impairment subtypes, but it does not test a treatment, cure, or prevention.
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Defects in phospholipase A(2) lead to a range of phenotypes.
Why it matters
This study found that mutations in the PLA2G6 gene cause childhood neurologic disorders and that some affected patients had Lewy bodies and neurofibrillary tangles. It concerns rare genetic childhood disorders, not Alzheimer's disease, and does not test any treatment for Alzheimer's.
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Triggering receptor expressed on myeloid cells 2 (TREM-2) is a membrane-bound receptor expressed by microglia and macrophages.
Why it matters
Found a soluble form of the TREM-2 protein in spinal fluid, with higher levels in people with multiple sclerosis and other inflammatory neurologic diseases than in people with non-inflammatory neurologic diseases. Blood levels did not differ between groups. The study looked at multiple sclerosis, not Alzheimer's.
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53/100
Patterns of gray matter loss are associated with neurofibrillary tangle (NFT) pathology, specifically with NFT burden at Braak stages III and IV and with Braak stage itself at higher stages.
Why it matters
In 83 people with Alzheimer-type tangle pathology at autopsy, compared with 20 people with little, brain scans taken during life showed more widespread gray matter loss at the most advanced tangle stages (Braak V and VI). At the middle stages (Braak III and IV) no loss was seen by stage alone, but people with a higher tangle burden had more loss in the temporal lobes. The authors conclude that MRI atrophy patterns are an "approximate" in-life indicator of the brain damage from Alzheimer pathology. This is a group-level association, not a diagnostic test or a treatment finding.
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It is important to distinguish FTLD from other neurodegenerative diseases like Alzheimer disease (AD), but this may be difficult clinically because of atypical presentations.
Why it matters
This study evaluated cerebrospinal fluid biomarkers in 30 patients with frontotemporal lobar degeneration and 19 with Alzheimer disease, using autopsy or genetic testing to confirm diagnoses. It is about distinguishing these diseases diagnostically and does not test any treatment, cure, or prevention.
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The risk of vascular or mixed dementia, but not of other types of dementia, was significantly increased in MCI patients with a large amount of subcortical hyperintensities at baseline.
Why it matters
In this study of 170 people with mild cognitive impairment, subcortical hyperintensities on MRI were not associated with developing dementia as a whole, including Alzheimer's disease. They were linked only to a higher risk of vascular or mixed dementia, so this does not support a way to prevent or treat Alzheimer's disease.
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TAR DNA-binding protein 43 (TDP-43) is the disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS).
Why it matters
In frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U) and ALS, TDP-43 — normally found in the cell nucleus — ends up in insoluble clumps. In cultured cells, this study found that blocking TDP-43 from entering or leaving the nucleus produced such clumps; a version that could not enter the nucleus also trapped the cell's own TDP-43 and drained it from the nucleus. The authors conclude only that these diseases "may be linked" to faulty TDP-43 transport; this is cell work, with no patients, Alzheimer's data or treatment tested.
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The hippocampus is the brain structure of highest and earliest structural alteration in Alzheimer's disease (AD).
Why it matters
This longitudinal imaging study found that hippocampal atrophy in mild cognitive impairment and Alzheimer's disease mainly involved the CA1 subfield, while increasing age in healthy people was mainly associated with subiculum atrophy. It helps distinguish normal aging from Alzheimer's-related brain change and does not test any treatment, cure or prevention.
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TAR DNA binding protein-43 (TDP-43) is the pathologic substrate of neuronal and glial inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTDL-U) and in amyotrophic lateral sclerosis (ALS).
Why it matters
This cell study found that progranulin mediates cleavage of TDP-43 and that suppressing progranulin leads to caspase-dependent accumulation of TDP-43 fragments. It is an early cell-culture 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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The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem disorder that severely damages predisposed nerve cell types in circumscribed regions of the human nervous system.
Why it matters
This lecture revisits a six-stage scheme in which Lewy body pathology in sporadic Parkinson's disease is proposed to start in the lower brainstem and olfactory areas, then involve the substantia nigra — when symptoms "probably" appear — and finally reach the neocortex. The scheme came from a cross-sectional study of 168 autopsy brains, so the order is inferred from different people rather than tracked in one person over time. It concerns Parkinson's, not Alzheimer's, and reports no treatment, cure or prevention.
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The triggering receptor expressed on myeloid cells 2 (TREM-2) delivers intracellular signals through the adaptor DAP12 to regulate myeloid cell function both within and outside the immune system.
Why it matters
This study in mice found that TREM-2 is expressed on macrophages and functions to restrain macrophage activation. It is an animal study and does not directly address treating, curing, or preventing Alzheimer's disease.
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DAP12 is an ITAM-containing adapter that associates with receptors in myeloid and NK cells.
Why it matters
A study in mouse macrophages finding that TREM-2, working through the adapter DAP12, sends an inhibitory signal that reduces TNF production triggered through TLRs and FcRs. Knocking down TREM-2 increased this TNF production, and the authors conclude TREM-2 and its ligand can reduce the inflammatory response. It does not study Alzheimer's disease.
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Patients with chronic schizophrenia displayed bilateral hippocampal volume reduction.
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In later-myelinating regions, the severity and rate of myelin breakdown in healthy older individuals are associated with APOE status and support the hypothesis that this process may contribute to age at onset of AD.
Why it matters
In a single MRI scan of 104 healthy people aged 55 to 75, older participants showed lower white-matter integrity (measured indirectly) in late-maturing frontal and corpus callosum regions, and this age-related drop was steepest in APOE4 carriers, intermediate in APOE3/3, and shallowest in APOE2 carriers; an early-maturing region showed no APOE difference. Because people were compared at one point in time rather than followed, this is an association, which the authors say "support[s] the hypothesis" that myelin breakdown "may contribute to age at onset of AD." No memory or dementia outcomes were measured.
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Alpha-synuclein (alpha-Syn) is enriched in nerve terminals.
Why it matters
In this mouse study, animals making mutant human alpha-synuclein developed nerve cell damage and death along with reduced activity of mitochondrial complex IV in the spinal cord. These findings come from genetically modified mice, not people, so they do not yet show how Parkinson's disease should be treated in patients.
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.
- Appoptosin-Mediated Caspase Cleavage of Tau Contributes to Progressive Supranuclear Palsy Pathogenesis
- Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation
- Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism
- Empagliflozin reduces kidney fibrosis and improves kidney function by alternative macrophage activation in rats with 5/6-nephrectomy
- TREM2/β-catenin attenuates NLRP3 inflammasome-mediated macrophage pyroptosis to promote bacterial clearance of pyogenic bacteria
- Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
- Docosahexaenoic acid and the aging brain
- “Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain”
- Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study