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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STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision.
Why it matters
Describes STAR, free open-source software for aligning RNA sequencing data. The authors report it maps reads more than 50 times faster than other aligners while improving sensitivity and precision.
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56/100
FUS/TLS (fused in sarcoma/translocated in liposarcoma) and TDP-43 are integrally involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Why it matters
In mouse and human brain, FUS/TLS bound RNAs from more than 5,500 genes, and depleting it from the adult nervous system altered the levels or splicing of more than 950 mRNAs, most distinct from RNAs dependent on TDP-43. Only 45 RNAs were reduced after depletion of either protein, including mRNAs from genes with exceptionally long introns, supporting a common loss-of-function pathway as one component underlying motor neuron death.
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Cerebral amyloid deposition is associated with APOE4 carrier status in older healthy control subjects and symptomatic AD patients, and increases with age in older cognitively normal individuals.
Why it matters
In florbetapir PET scans of 245 people aged 18–92, APOE4 carriers who were older and healthy, had mild cognitive impairment, or had Alzheimer dementia showed more amyloid than non-carriers, and amyloid rose with age only in the older healthy group. In cognitively normal adults amyloid began to increase around age 58, and the authors predicted that scans would typically turn amyloid-positive near age 56 in APOE4 carriers versus 76 in non-carriers. These are group-level estimates of when amyloid appears on a scan, not of when symptoms start, and the study tested no treatment.
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Inclusions composed of α-synuclein (α-syn), i.e., Lewy bodies (LBs) and Lewy neurites (LNs), define synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies (DLB).
Why it matters
In cultured primary neurons, lab-made alpha-synuclein fibrils entered the cells and pulled the neurons' own alpha-synuclein into clumps resembling the Lewy bodies and Lewy neurites seen in Parkinson's disease and dementia with Lewy bodies. The clumps formed without adding extra alpha-synuclein, appeared first in axons and then in the cell body, and were followed by loss of synaptic proteins, worsening nerve-cell signalling and connectivity, and eventually cell death. This is a cell-culture model the authors offer for testing future therapies. It is not a treatment, and it did not study Alzheimer's disease or people.
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Plasma sphingolipids have been shown to predict cognitive impairment and hippocampal volume loss, but there is little research in patients with Alzheimer's disease (AD).
Why it matters
This study looked at whether certain plasma sphingolipid levels could predict progression in people already diagnosed with Alzheimer's disease. It is about finding a possible marker of progression, not about treating, curing or preventing the disease.
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Amyloid-β oligomers may cause cognitive deficits in Alzheimer's disease by impairing neuronal NMDA-type glutamate receptors, whose function is regulated by the receptor tyrosine kinase EphB2.
Why it matters
In mice, reducing EphB2 impaired memory-related brain functions, and increasing EphB2 rescued cognitive functions in an Alzheimer's model. This is an animal study, so it does not show that targeting EphB2 would treat, cure, or prevent Alzheimer's disease in people.
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White matter hyperintensities predict an increased risk of stroke, dementia, and death.
Why it matters
This review of 46 long-term studies found that white matter hyperintensities seen on brain magnetic resonance imaging were associated with an increased risk of stroke, dementia, and death. The authors say finding them should prompt detailed screening for risk factors of stroke and dementia.
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Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative diseases with clinical and pathological overlap.
Why it matters
This review describes how mutations in TDP-43 and FUS/TLS cause ALS and frontotemporal lobar degeneration and how these RNA/DNA-binding proteins are linked to neurodegeneration. It redirects research toward RNA processing but reports no treatment, cure or prevention.
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Studies of post-mortem tissue have shown that the location of fibrillar tau deposits, called neurofibrillary tangles (NFT), matches closely with regions of massive neuronal death, severe cytological abnormalities, and markers of caspase activation and apoptosis, leading to the idea that tangles cause neurodegeneration in Alzheimer's disease and tau-related frontotemporal dementia.
Why it matters
Watching living tau mice (Tg4510) under a microscope, the researchers saw executioner caspases switch on "hours to days" before a tangle formed, and neurons that then formed tangles stayed alive with caspase activity seemingly suppressed. They propose that caspase cuts tau, and the cut tau pulls normal tau into tangles — making tangles "'off pathway' to acute neuronal death" rather than its direct cause. These are mouse findings; no treatment was tested.
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56/100
Neuronal accumulation of alpha-synuclein and Lewy body formation are characteristic to many neurodegenerative diseases, including Parkinson's disease (PD).
Why it matters
In cell cultures and a transgenic model of Parkinson's-like pathology, alpha-synuclein released by neurons was taken up by neighbouring cells "via endocytosis", formed Lewy-like inclusions, and was associated with signs of cell death; failure of lysosomes "promoted" this build-up. The authors present this as evidence for how Lewy pathology may spread from cell to cell in Parkinson's disease and "other proteinopathies". It is laboratory model work with no patients, no treatment tested, and no Alzheimer's-specific findings.
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Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown.
Why it matters
Imaging live Alzheimer's model mice, the researchers found that astrocytes — the brain's support cells — had raised resting calcium across their whole network, not just next to amyloid plaques, and fired calcium signals more often, in sync over long distances, and out of step with nearby neurons. Rare calcium waves that spread at least 200 micrometres were seen only in mice with plaques, starting near a plaque. This is mouse imaging work: it describes abnormal support-cell signalling, not a cause of the disease or a treatment for people.
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Logopenic progressive aphasia (LPA) is a distinctive variant of primary progressive aphasia.
Why it matters
Patients with the logopenic variant of primary progressive aphasia had slow speech, impaired sentence repetition and comprehension, and severe deficits in phonological loop tasks, with atrophy or reduced blood flow in specific left-brain language regions. Recent studies suggest Alzheimer disease may be the most common pathology underlying this clinical syndrome.
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The quantification of these alterations with (18)F-fluorodeoxyglucose PET may allow for the objective assessment of the progression and treatment of this disease manifestation.
Why it matters
This study found decreased prefrontal and parietal metabolism and abnormal metabolic network activity in people with Parkinson's disease who also had mild cognitive impairment. It concerns cognitive decline in Parkinson's disease rather than Alzheimer's disease, and it does not test any treatment.
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These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of alpha-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.
Why it matters
In brain tissue from people who had died, TDP-43 protein clumps were found in 71% of cases with hippocampal sclerosis and 23% of Alzheimer's disease cases. This suggests that some Alzheimer's cases have a pathology similar to frontotemporal lobar degeneration with ubiquitinated inclusions, but it is a tissue study and does not test treatment or prevention.
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Systemic inflammation is associated with ischemia and Alzheimer disease (AD).
Why it matters
In 1,926 Framingham Offspring participants aged 35 to 85 without stroke or dementia, higher blood levels of 10 inflammatory markers, taken as a group, were linked to smaller brain volume for head size (p < 0.0001), but not to white-matter lesions (p = 0.28). The authors say this is "consistent with the hypothesis that higher inflammatory markers are associated with greater atrophy than expected for age," but their cross-sectional data "cannot establish causality". The study does not show that lowering inflammation protects the brain or prevents Alzheimer's.
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Ubiquitin-positive tau-negative neuronal cytoplasmic inclusions and dystrophic neurites are common pathological features in frontotemporal lobar degeneration (FTLD) with or without symptoms of motor neuron disease and in amyotrophic lateral sclerosis (ALS).
Why it matters
This laboratory study identified TDP-43 as a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis, and found abnormal phosphorylation in accumulated TDP-43. It concerns these disorders rather than treating, curing or preventing Alzheimer's disease.
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Frontotemporal dementia and Alzheimer disease display different spatial distributions of hypoperfusion on arterial spin labeling MRI.
Why it matters
In 21 patients with frontotemporal dementia, 24 with Alzheimer disease, and 25 controls, arterial spin labeling MRI detected different patterns of reduced blood flow between the two dementias. This is a cross-sectional imaging study and does not test any treatment, though it may help distinguish these conditions.
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Why it matters
Reports that synaptic activity regulates amyloid-beta levels in brain interstitial fluid in vivo.
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Cholesterol-induced production of amyloid beta (Abeta) as a putative neurotoxin in Alzheimer's disease (AD), along with epidemiological evidence, suggests that statin drugs may provide benefit in treatment of the disorder.
Why it matters
In this trial, atorvastatin lowered circulating cholesterol and showed some positive signals on clinical measures, but the results varied by statistical method and did not show a clear, consistent clinical benefit. It does not establish statins as a treatment for Alzheimer's disease.
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Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases.
Why it matters
Live imaging showed that microglia, the immune cells of the brain, constantly survey their surroundings even in their presumed resting state. Damage to the blood-brain barrier made them switch quickly to shielding the injured site.
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In contrast to observations in individuals not treated with CART, we found no relationship between CSF markers and neurological status in this CART-using cohort with advanced HIV/AIDS.
Why it matters
In this cohort of patients with advanced HIV/AIDS receiving combination antiretroviral therapy, cerebrospinal fluid markers were not related to neurological status, unlike in people not treated with such therapy. This concerns HIV-associated neurological disease and does not address treating, curing, or preventing Alzheimer's disease.
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At autopsy the striatal dopaminergic transporter is reduced.
Why it matters
This imaging study compared a dopamine transporter scan with clinical diagnosis in 164 older people to help tell dementia with Lewy bodies apart from other dementias such as Alzheimer's disease. It is about improving diagnosis, not about treating, curing or preventing these diseases.
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Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers.
Why it matters
In a trial of 372 patients with mild to moderate Alzheimer's disease, meningoencephalitis (brain inflammation) occurred in 18 of 298 patients given the amyloid vaccine AN1792 (6%) and in none of 74 on placebo, and dosing was stopped. Twelve recovered to or close to baseline within weeks, while six were left with disabling cognitive or neurologic effects.
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Two substrates of insulin-degrading enzyme (IDE), amyloid beta-protein (Abeta) and insulin, are critically important in the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2), respectively.
Why it matters
Mice lacking the insulin-degrading enzyme (IDE) gene broke down less amyloid-beta and insulin, built up more amyloid-beta in the brain, and had high insulin levels and glucose intolerance. The authors suggest reduced IDE function may underlie or contribute to some forms of Alzheimer's disease and type 2 diabetes.
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This study traces the course of pathology in incidental and symptomatic Parkinson cases and proposes a staging procedure based upon the readily recognizable topographical extent of the lesions.
Why it matters
Describes a scheme for staging brain pathology in sporadic Parkinson's disease. It grades how far that pathology has spread and concerns Parkinson's disease rather than offering an Alzheimer's 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.
- Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians
- The predominant form of the amyloid beta-protein precursor in human brain is protease nexin 2
- TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in amyotrophic lateral sclerosis and frontotemporal dementia
- Neurofilament light chain and α-synuclein RT-QuIC as differential diagnostic biomarkers in parkinsonisms and related syndromes
- Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans
- PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment
- TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer's disease mice
- Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study
- Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43
- Development and External Validation of a Plasma p-tau217-Based Model for MCI-to-Dementia Progression