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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18 F-flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology.
Why it matters
This multicenter study found that the tau PET tracer 18F-flortaucipir showed elevated uptake in specific brain regions in patients with progressive supranuclear palsy compared with controls and Parkinson disease patients. It is an imaging study for distinguishing these conditions and does not test any treatment, cure, or prevention for Alzheimer disease.
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Neuronal inclusions of aggregated RNA-binding protein fused in sarcoma (FUS) are hallmarks of ALS and frontotemporal dementia subtypes.
Why it matters
FUS is a protein whose clumps inside nerve cells are a hallmark of ALS and some forms of frontotemporal dementia; this lab study found that adding phosphate groups to its sticky "low-complexity" region, or mutations that mimic them, made the protein less likely to phase-separate and aggregate. In human and yeast cells, the phosphate-mimicking version of FUS aggregated less and "can ameliorate FUS-associated cytotoxicity." The authors suggest this is a "potential treatment pathway amenable to pharmacologic modulation," but no drug was tested and the study did not look at Alzheimer's disease.
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Our review identified several measures of speech which may assist with diagnosis and classification, and consolidated the brain-behavior associations relating to speech in FTD, PPA, and progressive apraxia of speech.
Why it matters
This review found that speech measures may help diagnose and classify frontotemporal dementia, primary progressive aphasia and progressive apraxia of speech, but methods and naming varied between studies. It is about diagnosis and monitoring, not about treating, curing or preventing these conditions.
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Alterations in α-synuclein dosage lead to familial Parkinson's disease (PD), and its accumulation results in synucleinopathies that include PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA).
Why it matters
This review discusses how alpha-synuclein accumulation causes synucleinopathies and contributes to the fibrilization of amyloid-beta and tau, two key proteins in Alzheimer's disease. It describes mechanisms of neurodegeneration and reports no treatment, cure or prevention for Alzheimer's disease.
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Although mutations within the TREM2 gene have been robustly associated with Alzheimer's disease, it is not known whether alterations in the regulation of this gene are also involved in pathogenesis.
Why it matters
Across three independent cohorts, this study found increased DNA methylation near the TREM2 gene in the superior temporal gyrus of Alzheimer's disease brain. It identifies an epigenetic change associated with the disease but does not test any treatment, cure, or prevention.
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The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative diseases is a work in progress that is important for both clinicians and basic scientists.
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Haplodeficiency of the microglia gene TREM2 increases risk for late-onset Alzheimer's disease (AD) but the mechanisms remain uncertain.
Why it matters
In AD-like mice and human AD tissue, reduced TREM2 or DAP12 impaired microglial envelopment of amyloid deposits, leading to less compact plaques and axonal dystrophy. It describes a mechanism and does not test a treatment or cure.
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Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial.
Why it matters
In mice lacking progranulin, a gene linked to frontotemporal dementia (FTD), the brain's immune cells (microglia) made more complement proteins with age and removed more inhibitory synapses in the thalamus, which the authors link to overactive brain circuits and compulsive-like grooming. When the complement gene C1qa was also deleted, the authors report less synapse loss, neurodegeneration, abnormal behaviour and early death. The authors conclude that complement-driven synapse pruning is a major driver of progranulin-related neurodegeneration; this is a mouse study of FTD biology, not a test of any treatment or of Alzheimer's disease in people.
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Our data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding.
Why it matters
Using donated brain tissue, this lab study found that the tau scan tracer [F-18]-AV-1451 (T807) binds strongly to the tau tangles typical of Alzheimer's disease. It does not seem to bind amyloid, α-synuclein or TDP-43, and it binds less to the type of tau found in brains with non-Alzheimer tau diseases. The authors also found it binds to some non-tau targets, including melanin-containing cells and areas of bleeding. They say this matters for interpreting the tracer's signal on scans of living people, a question this tissue study did not test directly.
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The hexanucleotide repeat expansion (HRE) GGGGCC (G4C2) in C9orf72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
In a fly model and C9orf72 patient-derived neurons, the repeat expansion impaired nuclear import, and these deficits were rescued by small molecules and antisense oligonucleotides targeting the repeat RNA structures. This identifies nucleocytoplasmic transport defects as a possible pathway amenable to pharmacotherapeutic intervention, but it is early model-based work, not a treatment tested in patients.
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Cytoplasmic aggregation of TDP-43, accompanied by its nuclear clearance, is a key common pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD).
Why it matters
In mouse embryonic stem cells, loss of TDP-43 caused nonconserved cryptic exons to be spliced into messenger RNAs, often disrupting their translation, and forcing repression of these exons prevented cell death in TDP-43-deficient cells. Repression of cryptic exons was also impaired in ALS-FTD cases, suggesting this splicing defect could potentially underlie TDP-43 proteinopathy.
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The major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis is a G4C2 repeat expansion in C9ORF72.
Why it matters
A G4C2 repeat expansion in the C9ORF72 gene is, as this paper states, "the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis," and research had been held back by "a lack of animal models." The authors delivered 66 copies of the repeat into the mouse brain and spinal cord with a virus. By 6 months the mice showed RNA foci, dipeptide repeat protein inclusions, TDP-43 pathology, loss of cortical and Purkinje neurons, and behaviour the authors describe as similar to patient symptoms (hyperactivity, anxiety, antisocial behaviour, motor deficits). This is a mouse model of FTD/ALS, not of Alzheimer's disease, and it tests no treatment.
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Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury.
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The highly complex structure of the human brain is strongly shaped by genetic influences.
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In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions.
Why it matters
Presents DESeq2, a statistical method and software package for finding systematic changes in count data, such as RNA-seq read counts per gene, across experimental conditions. It is a general methods paper, not about Alzheimer's.
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Our data indicate that the APOE ε4 allele is an important predictor of cognitive function in PD across multiple domains.
Why it matters
Among patients with Parkinson disease, the APOE epsilon4 allele was associated with lower performance on several cognitive tests, while MAPT and SNCA variants were not associated with any test scores. This concerns cognition in Parkinson disease and does not provide a treatment or prevention for Alzheimer disease.
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57/100
CSF NFL differs among different neurodegenerative diseases and is especially high in dementias engaging subcortical brain regions, such as VaD and mixed AD and VaD, but also in frontotemporal dementia.
Why it matters
In 3,356 people with dementia in Swedish registries, spinal-fluid neurofilament light (NFL) was highest in frontotemporal dementia, vascular dementia and mixed Alzheimer's/vascular dementia, and lowest in Alzheimer's that began before 65. Across all diagnoses, and particularly in Alzheimer's, higher NFL went with lower MMSE scores and, in a subset of 478 people, shorter survival. The authors say this supports high NFL as a sign of more aggressive disease; it is a correlation, not a diagnostic test for Alzheimer's or a treatment.
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A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
This laboratory study describes how a repeated stretch of DNA in the C9orf72 gene folds into unusual shapes and triggers molecular events that may lead to ALS and frontotemporal dementia. It provides a model for how these repeats cause disease but does not test any treatment in patients.
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57/100
We examined regional distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in frontotemporal lobar degeneration (FTLD).
Why it matters
This autopsy study of 39 brains found that a protein called pTDP-43 spreads through the brain in four patterns that seem to follow a sequence in a type of frontotemporal dementia. This describes how the disease progresses but does not test any treatment, so it does not yet show how to treat, cure or prevent dementia.
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57/100
The finding that a GGGGCC (G4C2) hexanucleotide repeat expansion in the chromosome 9 ORF 72 (C9ORF72) gene is a common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) links ALS/FTD to a large group of unstable microsatellite diseases.
Why it matters
This study found that in people with C9orf72-related ALS and frontotemporal dementia, the repeated DNA is read in both directions and produces unusual proteins that build up in affected brain regions. It suggests these findings could lead to new biomarkers and treatments, but this is tissue-based research and not a therapy tested in patients.
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Abnormal forms of prion protein that were found in multiple peripheral tissues were associated with diarrhea, autonomic failure, and neuropathy.
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A causative association was recently demonstrated between homozygous TREM2 mutations and frontotemporal dementia (FTD)-like syndrome and between heterozygous TREM2 exon2 genetic variations and late-onset Alzheimer's disease (AD).
Why it matters
This study asked whether carrying one altered copy of the TREM2 gene is linked to the risk of frontotemporal dementia (FTD). It read part of the gene (exon 2) in 1,030 people, 352 with FTD, 484 healthy controls and 194 with Alzheimer's disease, and found 8 different missense or nonsense mutations in 24 of them. This record does not say how those 24 carriers were split between the groups, so it does not show whether the mutations were more common in FTD, and it does not test any treatment or prevention.
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A hexanucleotide GGGGCC repeat expansion in the noncoding region of the C9ORF72 gene is the most common genetic abnormality in familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
In this laboratory study using patient-derived neurons, a repeated stretch of DNA in the C9orf72 gene caused toxic RNA clumps and other problems, which were reduced with antisense oligonucleotide therapeutics. This points to a possible treatment approach for C9orf72-related ALS and frontotemporal dementia, but it is early cell-based research, not a proven therapy in patients.
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We assessed whether expansion size is associated with disease severity or phenotype.
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Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs.
Why it matters
In 226 people with cognitive impairment, amyloid burden was linked only to lobar microbleeds, while markers of small vessel disease were linked to both lobar and deep microbleeds. This helps explain different causes of microbleeds but does not offer a 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.
- TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis
- ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43
- Tau in physiology and pathology
- DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features
- The mouse homolog of the human amyloid beta protein (AD-AP) gene is located on the distal end of mouse chromosome 16: further extension of the homology between human chromosome 21 and mouse chromosome 16
- [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data
- Differential expression of conditioned medium from tauopathies patients' olfactory neuroepithelial precursor cells, implications in the neurodegeneration
- TREM2 Promotes Microglial Survival by Activating Wnt/β-Catenin Pathway
- Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss
- Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group