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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A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord 1 .
Why it matters
UNC13A gene variants are among the strongest genetic risk signals for FTD and ALS, but how they raise risk was unknown. In human brain tissue, neuronal cell lines and stem-cell-derived motor neurons, this study found that losing the protein TDP-43 from the nucleus lets a "cryptic exon" into UNC13A's RNA and lowers UNC13A protein, and that the top risk variants, located next to that exon, increase this mis-splicing when TDP-43 is not working. It is lab evidence linking a genetic risk factor to TDP-43 loss in FTD and ALS. It does not study Alzheimer's disease and tests no treatment.
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Variants of UNC13A, a critical gene for synapse function, increase the risk of amyotrophic lateral sclerosis and frontotemporal dementia 1-3 , two related neurodegenerative diseases defined by mislocalization of the RNA-binding protein TDP-43 4,5 .
Why it matters
TDP-43 depletion causes a cryptic exon to be included in UNC13A, leading to loss of UNC13A protein, and common risk variants overlap with TDP-43 binding sites and worsen this. The authors call this a promising therapeutic target, but no treatment has been tested.
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The genetic basis of Lewy body dementia (LBD) is not well understood.
Why it matters
Whole-genome sequencing in large cohorts identified five risk loci for Lewy body dementia and implicated mutations in the gene GBA, and genetic risk scores showed shared risk with Alzheimer's and Parkinson's diseases. This improves understanding of the genetic architecture of Lewy body dementia but reports no treatment or cure.
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64/100
Increased α-synuclein egress in serum neuronal exosomes precedes the diagnosis of Parkinson's disease, persists with disease progression and in combination with clusterin predicts and differentiates Parkinson's disease from atypical parkinsonism.
Why it matters
In this cross-sectional study of 664 serum samples, neuron-derived exosomal α-synuclein was increased twofold in prodromal and clinical Parkinson's disease compared with multiple system atrophy, controls, or other neurodegenerative diseases, and remained stably elevated with disease progression. This suggests a possible blood test for Parkinson's disease, but it does not report a treatment, cure, or prevention for Alzheimer's disease.
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While APOEε4 is associated with increased amyloid-β burden, its association with cerebral tau pathology has been controversial.
Why it matters
APOE ε4 was associated with increased tau PET uptake in the entorhinal cortex and hippocampus independently of amyloid-β, sex, age and clinical status. The authors suggest APOE ε4 as a potential target for future disease-modifying trials targeting tau pathology, but no treatment was tested.
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With the potential development of new disease-modifying Alzheimer's disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment.
Why it matters
In this 2020 study, levels of a blood protein, plasma pTau181, were 3.5 times higher in people with Alzheimer's disease than in controls. The test separated Alzheimer's from frontotemporal lobar degeneration with an area under the curve of 0.894 against clinically diagnosed cases and 0.878 against autopsy-confirmed cases, and it also identified people who were amyloid-PET-positive and correlated with tau-PET. The authors propose it as a cheaper, less invasive screen to decide which people with cognitive or behavioural symptoms should go on to fuller testing, not as a stand-alone diagnosis. The record does not report sample sizes, cut-offs or limitations.
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Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis.
Why it matters
By profiling more than 100,000 single cells from healthy and cirrhotic human liver, this study reports a scar-associated TREM2+CD9+ macrophage group that expands in liver fibrosis, comes from circulating monocytes and is described as pro-fibrogenic. It also reports ACKR1+ and PLVAP+ blood-vessel cells that gather in the scarred areas. It is a liver study that tested no treatment and says nothing directly about Alzheimer's disease; its relevance here is that it describes TREM2-carrying immune cells in human tissue.
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APOE ε4 count was associated with higher TDP-43 proteinopathy stage (odds ratio [OR] 2·0, 95% CI 1·6-2·6; p=1·9 × 10 -9 ) and TDP-43 burden (0·40, 0·28-0·52; p=1·2 × 10 -10 ).
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64/100
These results support the hypothesis that the appearance of WMH follows age and disease-dependent regional distribution patterns, potentially influenced by differential underlying pathophysiologic mechanisms, and possibly with a differential link to vascular and neurodegenerative changes.
Why it matters
In MRI scans of 1,836 German adults, with follow-up scans of 307 older US adults, white matter lesions clustered in four distinct regions. Lesions near the front of the brain's fluid spaces appeared earliest, in the fifth decade of life, and were associated with higher systolic blood pressure and with shrinkage in Alzheimer's-related areas. A different, "dorsal" pattern was associated with an Alzheimer's polygenic risk score in older people and with cognitive decline. These are associations, not proof of cause, but they suggest different lesion locations may reflect different vascular and neurodegenerative processes.
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It is associated with metabolic syndrome, incident diabetes, carotid atherosclerosis, and endothelial dysfunction, conditions that in turn are strongly linked with brain damage and cognitive impairment.
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More-severe diabetes (defined by higher HbA 1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology.
Why it matters
More-severe diabetes, defined by higher HbA1c and longer disease duration, was associated with smaller total and regional brain volumes and an increased burden of white matter hyperintensities, but prediabetes and less-severe diabetes were not. This suggests that more severe diabetes, rather than prediabetes, is linked to brain volume loss and vascular pathology.
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Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline.
Why it matters
In mouse models of Alzheimer's, this study reports that the complement protein C1q was increased and associated with synapses before overt plaque deposition. Blocking C1q, C3 or the microglial receptor CR3 reduced both the number of phagocytic microglia and the extent of early synapse loss. The authors argue that complement and microglia act early in the disease, not only through late-stage inflammation. These are mouse results with no human data and no reported memory outcomes, so they point to a research target, not a treatment.
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Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus.
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Identifying a clinical distinction between the invariably lethal prion disease Creutzfeldt-Jakob disease (CJD) and nonprion rapidly progressive dementias is important and sometimes difficult; thus, reliable tools for diagnosis are in great demand.
Why it matters
This retrospective cohort study tested how well cerebrospinal fluid total tau, phosphorylated tau, and their ratio distinguish Creutzfeldt-Jakob disease from other rapidly progressive dementias. It is about diagnosis of a prion disease, not about treating, curing, or preventing Alzheimer disease.
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Better sleep consolidation attenuates the effect of APOE genotype on incident AD and development of neurofibrillary tangle pathology.
Why it matters
In this cohort study, better sleep consolidation weakened the link between the APOE epsilon 4 allele and the risk of developing Alzheimer disease and tau tangle density. It suggests sleep may modify genetic risk but does not show that improving sleep prevents or treats the disease.
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Homozygous mutations in exon 2 of TREM2, a gene involved in Nasu-Hakola disease, can cause frontotemporal dementia (FTD).
Why it matters
In a Belgian sample, rare TREM2 variants were enriched in both Alzheimer's disease and frontotemporal dementia patients compared with controls, most notably in the extracellular IgV-set domain. This identifies genetic risk associations only and does not show any way to treat, cure or prevent Alzheimer's disease.
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Semantic cognition requires a combination of semantic representations and executive control processes to direct activation in a task- and time-appropriate fashion [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison.
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An international working group from the Centres of Excellence in Neurodegeneration completed a structured process to develop definitions and imaging standards for markers and consequences of cerebral small vessel disease (SVD).
Why it matters
Sets out neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Shared standards make imaging studies comparable with one another; they do not themselves treat or prevent disease.
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TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00257712.
Why it matters
In this 20-week substudy of 30 adults, GHRH administration increased GABA levels in all three brain regions, increased NAAG in the frontal cortex, and decreased myo-inositol in the posterior cingulate. These are neurochemical changes in a small sample and do not show clinical benefit for treating or preventing Alzheimer's disease.
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The aim of this multicenter randomized controlled trial was to determine whether the incidence of dislocation one year after total hip arthroplasty is significantly lower in association with the use of a 36-mm femoral head articulation as compared with a 28-mm articulation.
Why it matters
This randomized controlled trial tested whether a larger femoral head reduces dislocation after total hip arthroplasty, which has nothing to do with Alzheimer's disease. It provides no information about treating, curing or preventing Alzheimer's disease.
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There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis.
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Recent genetic and proteomic studies demonstrate that clusterin/apolipoprotein-J is associated with risk, pathology, and progression of Alzheimer's disease (AD).
Why it matters
This study found that plasma clusterin concentration was associated with rates of brain atrophy in people with mild cognitive impairment compared to controls. The findings describe a potential biomarker for disease progression but do not test any treatment or prevention.
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The meta-analyses revealed structural brain abnormalities in MDD that are distinct from those observed in BD.
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Metabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort.
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Previous small studies and case reports have suggested that neurological disorders may be associated with bullous pemphigoid (BP).
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.
- Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease
- Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease
- TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination
- A biophysical and molecular characterization of the interaction between the Alzheimer risk factor BIN1 and the neuronal scaffold protein p140Cap
- TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42 in HMC3 cells
- Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins
- Astrocyte infection by HIV-1: mechanisms of restricted virus replication, and role in the pathogenesis of HIV-1-associated dementia
- Progress of radiomics research on white matter hyperintensity lesions
- Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases
- A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests