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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The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer's disease (AD), reflective of a central role for myeloid cells in neurodegeneration.
Why it matters
In mice engineered to carry one copy of the TREM2 R47H variant, a variant the authors describe as conferring "greatly increased risk" for Alzheimer's disease, the researchers report lower Trem2 mRNA, less TREM2 around amyloid plaques, and fewer immune (myeloid) cells gathered around plaques at 4 months of age. The authors describe these as "loss-of-function-like" effects; the record does not report what was found for plaque burden or nerve-fibre damage. This is a mouse study, it does not show how the variant behaves in people, and it tested no treatment.
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Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF).
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Neurodegenerative diseases likely share common underlying pathobiology.
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Variants of TREM2 are associated with Alzheimer's disease (AD).
Why it matters
In 5xFAD mice, raising TREM2 gene dosage reduced amyloid burden and changed microglial and neuronal gene expression. This is animal work, so it does not show that increasing TREM2 helps people with Alzheimer's.
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53/100
A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia, but it remains unclear how dietary salt harms the brain.
Why it matters
In mice, a high-salt diet impaired cerebral blood flow and endothelial function and led to cognitive impairment through a gut-initiated immune response involving TH17 cells and IL-17. This is animal research identifying a possible mechanism and a putative target, not evidence that reducing salt prevents dementia in people.
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53/100
[ 18 F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis.
Why it matters
In this clinical sample, tau PET and CSF p-tau both distinguished β-amyloid-positive Alzheimer disease from non-Alzheimer conditions well, and tau PET was associated with CSF biomarkers, most strongly p-tau. Within Alzheimer disease, Mini-Mental State Examination scores were associated with tau PET but not CSF biomarkers.
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In DLB, α-synuclein is an important predictor of disease duration, both independently and synergistically with tau and Aβ.
Why it matters
In 49 patients with dementia with Lewy bodies, alpha-synuclein was an important predictor of how long the illness lasted, alone and together with tau and amyloid. It is about disease duration in Lewy body dementia and does not test any treatment, cure or prevention.
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Sequence variations occurring in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) support an essential function of microglia and innate immunity in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders.
Why it matters
Using mass spectrometry, this laboratory study mapped where TREM2 (the "triggering receptor expressed on myeloid cells 2", which the authors tie to microglia and innate immunity in Alzheimer's) is cut and released from the cell surface: ADAM-family enzymes cut it just after amino acid histidine 157. That is the same position as p.H157Y, a variant the authors describe as Alzheimer-associated and found in the Han Chinese population, and the title says the variant "affects shedding and phagocytic function", although the stored record does not say in which direction. It is basic protein research with no patients and no treatment tested, so it explains a mechanism rather than showing a risk test or therapy.
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Using a cross-sectional design, we examined retinal structure in 38 consecutively enrolled patients with FTD and 44 controls using a standard SD-OCT protocol.
Why it matters
Using optical coherence tomography, this cross-sectional study compared retinal structure in 38 patients with frontotemporal degeneration and 44 controls. It concerns a possible retinal marker for frontotemporal degeneration, not the treatment, cure, or prevention of Alzheimer's disease.
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TREM2 variants have been identified as risk factors for Alzheimer's disease (AD) and other neurodegenerative diseases (NDDs).
Why it matters
This 2017 review pulls together research on TREM2, a gene for a receptor found only on immune cells, whose variants are linked to a higher risk of Alzheimer's and other neurodegenerative diseases. The authors argue this shows the immune response can play an active part in these diseases, and say the variants carry the highest Alzheimer's risk of any risk factor found in the previous two decades. They suggest studying TREM2 could lead to new tests and immune-based treatments, but the review reports no new data and no treatment.
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See Mercado and Hetz (doi:10.1093/brain/awx107) for a scientific commentary on this article.
Why it matters
In mouse models of neurodegeneration, two existing drugs, trazodone and dibenzoylmethane, restored memory deficits, prevented neurodegeneration and prolonged survival by acting on a pathway overactivated in Alzheimer's disease. These are early animal findings, so it is not yet known whether these drugs help people with Alzheimer's disease.
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Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD).
Why it matters
People who inherit two copies of the TREM2 p.T66M mutation develop an FTD-like syndrome, and this study built a gene-edited mouse carrying it to learn how. In the mice, the mutant Trem2 protein built up inside cells in an immature form and less soluble Trem2 was made, "similar to patients with the homozygous p.T66M mutation"; the mice were slower to resolve an inflammation triggered with a bacterial toxin, and their cultured macrophages were less able to engulf material — findings the authors describe as consistent with loss of function. This is mouse and cell work on a frontotemporal-dementia mutation; it does not test a treatment and does not show how TREM2 affects Alzheimer's disease in people.
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From the 144 participants (56.3% female and 43.7% male, with a mean [standard deviation] age of 80.7 [7.7] years), 118 participants were available for final follow-up.
Why it matters
In 144 people with early-stage Alzheimer's or mixed Alzheimer's/vascular disease from 24 day care centers in The Netherlands, higher levels of advanced glycation end products (AGEs) were associated with paratonia, a type of muscle stiffness in dementia (odds ratio 3.47). The authors suggest AGEs may contribute to paratonia by making tissues less elastic. Whether lowering AGE levels could delay this stiffness still needs to be tested.
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Amyloid precursor protein (APP) gives rise to the amyloid-β peptide and thus has a key role in the pathogenesis of Alzheimer disease.
Why it matters
This review summarizes what is known about the normal physiological functions of APP and related proteins, based on studies of knockout mice. It highlights that APP has important roles beyond amyloid production, which matters for understanding the safety of treatments that target it.
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Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses.
Why it matters
In 95 people from a registry, this cross-sectional study examined whether a polygenic risk score based on APOE4, CLU and ABCA7 was associated with cerebrospinal fluid Alzheimer biomarkers and whether cardiorespiratory fitness modified that association. It is cross-sectional, so it cannot show that exercise prevents Alzheimer's disease.
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Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality.
Why it matters
This record describes the protocol for the PANACEA trial, a randomised study testing whether giving N-acetylcysteine (NAC) around the time of surgery reduces cognitive changes after surgery compared with placebo. The background notes that some cognitive decline follows surgery in as many as one quarter of elderly surgical patients. Results are not included in this record.
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To determine if proton magnetic resonance spectroscopy ((1)H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used (1)H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls.
Why it matters
This study found that certain brain metabolites measured by magnetic resonance spectroscopy differ in adults with Down syndrome who have dementia compared to those without. It suggests these measures may be useful for diagnosis in future studies, but it does not test any treatment or cure.
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An intronic expansion of GGGGCC repeats within the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD).
Why it matters
In this laboratory study, C9ORF72 was found to control autophagic flux, and its depletion in neurons partly impaired autophagy and caused accumulation of TDP-43 and P62 aggregates. Loss of C9ORF72 alone had only a partial effect on neuron survival but synergized with Ataxin-2 Q30x toxicity to cause motor neuron dysfunction and cell death, suggesting a double-hit mechanism in ALS-FTD rather than a treatment.
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At baseline, worse olfaction (lowest tertile) was associated with more severe NMS, including anxiety and autonomic symptoms.
Why it matters
In people with early Parkinson's disease, worse baseline sense of smell was associated with long-term cognitive decline and progression to mild cognitive impairment. This concerns Parkinson's disease and does not test any treatment.
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The past decade has witnessed a revolution in our understanding of microglia.
Why it matters
This work describes a 'dark microglia' phenotype found mainly in pathological states such as chronic stress, aging and disease. It is an observational ultrastructural finding and does not test any Alzheimer's treatment.
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53/100
We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults.
Why it matters
In 535 older participants who underwent annual cognitive assessments and brain autopsy, higher brain BDNF gene expression was associated with slower cognitive decline. This is an observational association study and does not report any treatment, cure or prevention for Alzheimer's disease.
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53/100
We recently revealed that p.H157Y (rs2234255), a rare coding variant of triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated with Alzheimer's disease (AD) susceptibility in Han Chinese.
Why it matters
Combining data on 7,102 cases and 7,408 controls, this meta-analysis found the rare TREM2 variant p.H157Y was associated with higher Alzheimer's risk (OR=3.65). Earlier sequencing studies had reported no link, so the pooled result helps settle the question. The authors say it further establishes TREM2 as an important susceptibility gene for Alzheimer's.
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Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT.
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Diagnoses of dementia, probable AD, and MCI in 636 autopsied subjects from the Religious Order Study and the Rush Memory and Aging Project were based on clinical evaluation and cognitive performance tests.
Why it matters
In this study of 636 autopsied subjects, hippocampal sclerosis was more common in those over 90 years old and was assessed alongside TDP-43 and other age-related pathologies, dementia, and cognitive measures. It is an autopsy association study and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Microglia contribute to development, homeostasis, and immunity of the CNS.
Why it matters
This work concerns how TREM2 supports microglial expansion during aging and after demyelination, and notes that inactivating TREM2 mutations cause the early-onset dementia Nasu-Hakola disease. It is basic biology and does not test a therapy 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.
- Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies
- Tau-based therapies in neurodegeneration: opportunities and challenges
- Hippocampal volume and functional connectivity changes during the female menstrual cycle
- Progressive neurodegeneration in C. elegans model of tauopathy
- Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline
- Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature
- Biomarkers in Contrast-Induced Nephropathy: Advances in Early Detection, Risk Assessment, and Prevention Strategies
- The role of DYRK1A in neurodegenerative diseases
- Inflammasomes in neuroinflammation and changes in brain function: a focused review
- Hippocampal volumetric and morphometric studies in frontal and temporal lobe epilepsy