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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Neurodegenerative disorders are characterized by progressive loss of selectively vulnerable populations of neurons, which contrasts with select static neuronal loss because of metabolic or toxic disorders.
Why it matters
This review describes how abnormal protein conformers in neurodegenerative disorders may spread from cell to cell along anatomically connected pathways. It is a summary of human pathology and experimental evidence, not a study of any treatment, cure or prevention.
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Tauopathies are a broad set of neurodegenerative dementias characterized by aggregation of the tau protein into filamentous inclusions that can be found in neurons and glial cells.
Why it matters
This review describes activated microglia, astrocytes and proinflammatory molecules as hallmarks in brain regions affected by tau pathology in tauopathies including Alzheimer's disease. It reports no treatment, cure or prevention.
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The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Why it matters
In mouse motor neurons derived from embryonic stem cells, the RNA-binding protein FUS controlled production of circular RNAs, and some were altered in human stem cell-derived motor neurons carrying the FUS P525L mutation. This is laboratory cell work on how FUS mutations may act, not a treatment or prevention.
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Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed in microglia in the brain.
Why it matters
Soluble TREM2, a fragment of a microglial immune receptor, is raised in early Alzheimer's, but what it does was unknown. This study reports that it helped microglia survive and triggered inflammatory signals, and that versions carrying Alzheimer's risk mutations were "less potent" at both. The record does not describe the model or give effect sizes, and it shows nothing about treating or preventing Alzheimer's in people.
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Our study supports the usefulness of [ 18 F]AV1451 to characterize tau pathology in at least a subset of pathogenic MAPT mutations.
Why it matters
In one patient with a specific MAPT mutation causing frontotemporal dementia, tau PET scan results matched the distribution of tau pathology found after death. This is a single-case comparison of an imaging tracer with autopsy findings and does not test any treatment for Alzheimer's disease.
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This article presents the revised consensus criteria for the diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) based on an international research workshop on frontotemporal dementia (FTD) and ALS held in London, Canada in June 2015.
Why it matters
These revised consensus criteria describe frontotemporal dysfunction in amyotrophic lateral sclerosis as falling along a spectrum, affecting over 50% of persons with ALS and adversely impacting survival when present. They concern diagnosis and classification only and report no treatment, cure, or prevention.
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Neurogenic orthostatic hypotension (nOH) is common in patients with neurodegenerative disorders such as Parkinson's disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, and peripheral neuropathies including amyloid or diabetic neuropathy.
Why it matters
This consensus panel paper provides recommendations for screening, diagnosing, and treating neurogenic orthostatic hypotension and associated supine hypertension, conditions common in several neurodegenerative disorders including dementia with Lewy bodies. It is a set of expert recommendations rather than a study of a treatment that changes the course of Alzheimer's disease.
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The American Heart Association's LS7 score identified individuals who were vulnerable to multiple chronic nonvascular conditions.
Why it matters
In 6,506 middle-aged and older adults, higher Life's Simple 7 scores were linked to lower rates of noncardiovascular disease events, including dementia. This is an observational study, so it suggests improving cardiovascular health may reduce disease burden but cannot prove cause and effect.
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In this study, serum DHA levels were associated with pathogenesis of cerebral amyloidosis and with preservation of entorhinal and hippocampal volumes.
Why it matters
In this cross-sectional study of 61 participants, lower serum DHA levels were associated with cerebral amyloidosis and higher serum DHA was associated with greater brain volume in some regions. Because it is cross-sectional, it cannot show whether DHA causes or prevents amyloid deposition or brain changes.
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54/100
Expansion of a hexanucleotide repeat GGGGCC (G 4 C 2 ) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
Arginine-containing dipeptide repeat proteins polyGly-Arg and polyPro-Arg interacted with RNA-binding proteins and proteins with low complexity sequence domains that often mediate assembly of membrane-less organelles, and genetic analysis in Drosophila demonstrated the functional relevance of these interactions to dipeptide repeat toxicity. The proteins altered phase separation of low-complexity-domain-containing proteins, changing the material properties of these assemblies and perturbing the dynamics and/or functions of multiple membrane-less organelles.
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Alzheimer's disease (AD) neuropathology is associated with neuroinflammation, but there are few useful biomarkers.
Why it matters
This study built a new lab test (an ELISA) for soluble TREM2, a fragment of a microglial immune receptor found in spinal fluid, and used it to look at whether it could serve as an Alzheimer's biomarker in two groups: 100 people with Alzheimer's, mild cognitive impairment or in a control group, and a further 50 people with Alzheimer's or in a control group. The stored summary ends before the results, so it does not say whether levels differed between groups. It is a measurement study and does not test any treatment.
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Hexanucleotide expansions in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia.
Why it matters
In mice, a single dose of antisense oligonucleotides targeting repeat-containing C9ORF72 RNAs reduced RNA foci and dipeptide-repeat proteins and improved behavioral deficits. This identifies gain of toxicity from the repeat expansion as a disease mechanism and supports testing ASO-mediated therapy in people, though the work was done in mice.
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These findings support the view that chronic financial pressures associated with low income exert a weathering effect that results in premature aging.
Why it matters
In this longitudinal study of 100 Black middle-aged women, low income was robustly associated with accelerated biological aging on an epigenetic measure, not explained by health behaviors such as diet, exercise, smoking or alcohol. It links economic hardship to premature aging but does not test any treatment or prevention for Alzheimer's disease.
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This review summarizes the expression, post-translational modifications, and functions of tau in physiology and pathophysiology.
Why it matters
A review of tau in physiology and disease.
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In cohort 1, PVEC increased the effect on AD-versus-HC discrimination from a Cohen d value of 1.68 to 2.0 for composite SUVRs and from 0.04 to 1.04 for mesial temporal cortex SUVRs.
Why it matters
Applying partial-volume effect correction improved discrimination between Alzheimer disease patients and healthy controls on 18F-florbetaben amyloid PET, and the correction's effect correlated with brain atrophy. This is a technical imaging analysis method, not a treatment, cure or prevention of Alzheimer's disease.
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Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia.
Why it matters
This laboratory study found that apolipoprotein E binds with high affinity to TREM2 and that this binding increases microglial phagocytosis of apoptotic cells, while an Alzheimer's-associated TREM2 mutant showed vastly reduced binding. It identifies a molecular link between two proteins linked to Alzheimer's risk, but it is a biochemical and cell study and does not establish a treatment.
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We provide evidence that 2 common variants within the TREM locus are associated with pathological features of AD and aging-related cognitive decline.
Why it matters
This genetic study found that a variant in TREM1 was associated with more neuritic plaques, diffuse plaques, and amyloid density, and with faster cognitive decline. A separate variant near TREM2 was associated with more tau tangles and faster cognitive decline, suggesting these variants may influence Alzheimer's pathology.
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Since increased BBB permeability is found in tauopathies without Aß pathology, like PSP, we suspected that tau accumulation alone could not only be sufficient, but even more important than Aß for BBB damage.
Why it matters
In a mouse model of tauopathy, removing tau prevented progressive damage to the blood-brain barrier. This is an animal study, so it is early and preliminary, and it does not show that the same approach would work or be safe in people.
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54/100
In Alzheimer’s disease (AD), β-amyloid (Aβ) plaques are tightly enveloped by microglia processes, but the significance of this phenomenon is unknown.
Why it matters
In Alzheimer's mouse models, microglia wrapped around amyloid plaques acted as a barrier that limited plaque expansion, while plaque areas not covered by microglia formed protofibrillar Aβ42 hotspots associated with more severe axonal dystrophy. Microglia coverage was reduced with ageing, and the authors suggest failure of this barrier may be a target for new therapies and imaging.
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TDP-43 pathology is a disease hallmark that characterizes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP).
Why it matters
In laboratory and cell experiments, acetylation of TDP-43 reduced its RNA binding and promoted insoluble, hyper-phosphorylated clumps resembling those seen in ALS and FTLD-TDP, and acetylated TDP-43 lesions were found in ALS patient spinal cord. The authors suggest modulating acetylation as a possible strategy, but no treatment was tested in patients.
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This protocol describes a primary neuronal model of formation of α-synuclein (α-syn) aggregates that recapitulate features of the Lewy bodies and Lewy neurites found in Parkinson's disease brains and other synucleinopathies.
Why it matters
This protocol describes a laboratory model where adding preformed alpha-synuclein fibrils to neurons causes them to form clumps similar to those in Parkinson's disease and other synucleinopathies. It allows researchers to study how these clumps form and affect neurons and to test potential therapies, but it is a cell-based method, not a treatment.
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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43).
Why it matters
In cell and mouse neuron models, compounds that stimulate autophagy improved clearance of the TDP43 protein and enhanced survival of neurons carrying mutant TDP43. These are early laboratory findings, not results from human trials, so it is not yet known whether this approach would help patients.
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The triggering receptor expressed on myeloid 2 (TREM2) is an immune phagocytic receptor expressed on brain microglia known to trigger phagocytosis and regulate the inflammatory response.
Why it matters
In this genetic study of 2082 Alzheimer disease cases and 1648 cognitively normal controls, two TREM2 variants, p.R47H and p.R62H, were significantly associated with disease risk, and gene-based tests showed variants in TREM2 were genome-wide significantly associated with Alzheimer disease. This identifies TREM2 as a risk gene but does not provide a treatment, cure, or prevention.
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Massive GGGGCC repeat expansion in the first intron of the gene C9orf72 is the most common known cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS).
Why it matters
Using antibodies, this study found that both sense and antisense repeats of the expanded C9orf72 hexanucleotide are translated into aggregating dipeptide-repeat proteins in patient tissue. It describes a disease mechanism and does not test any treatment, cure or prevention.
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54/100
Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of frontotemporal dementia and motor neuron disease.
Why it matters
This study characterized new antibodies against dipeptide repeat proteins and analyzed their pathology in cases with C9ORF72 mutations, which cause frontotemporal dementia and motor neuron disease. It concerns those conditions, not Alzheimer's disease, and does not test any treatment, cure, or prevention for Alzheimer's.
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.
- Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease
- Reduced CSF p-Tau181 to Tau ratio is a biomarker for FTLD-TDP
- TREM2 Regulates the Removal of Apoptotic Cells and Inflammatory Processes during the Progression of NAFLD
- Olfaction in People with Down Syndrome: A Comprehensive Assessment across Four Decades of Age
- The Role of Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment
- TREM2 sustains microglial expansion during aging and response to demyelination
- The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models
- The neuropathology of chronic traumatic encephalopathy
- Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease
- ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice