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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This manuscript is the second part of a two-part description of the current status of understanding of the network function of the brain in health and disease.
Why it matters
This review discusses how brain network analysis methods can be applied to understand various neurological and psychiatric disorders, including Alzheimer's disease. It is a general overview of methods and does not test any specific treatment, cure, or prevention.
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In blood from C9orf72 expansion carriers, we found elevated methylation levels, reduced expression levels, and unstable expansions that tend to contract in successive generations, arguing against anticipation.
Why it matters
In blood from C9orf72 expansion carriers, this study found elevated methylation, reduced C9orf72 expression, and repeat expansions that tended to contract across generations. These are biological observations about a genetic cause of dementia and do not provide a treatment, cure, or prevention.
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Age-related hearing impairment (ARHI) is the most common sensory impairment in the aging population; a third of individuals are affected by disabling hearing loss by the age of 65.
Why it matters
This genome-wide association study identified 44 independent genomic loci for self-reported hearing difficulty, with gene sets enriched in auditory, nervous system, inner ear and cognitive processes. It provides insight into the genetics of hearing loss, which has been identified as a dementia risk factor, but does not test whether treating hearing loss prevents dementia.
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Microglia are resident macrophages of the CNS that are involved in its development, homeostasis and response to infection and damage.
Why it matters
This review describes microglia as having protective and regenerative functions, most prominently in supporting regeneration of myelin after injury, a process relevant to disorders including Alzheimer's disease. It reports no treatment or prevention result for Alzheimer's disease.
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We place these findings in the context of the selective, but by no means unique, involvement of BFCNs and their trophic dependence on NGF signaling and speculate as to how pathogenesis in these neurons is initiated, amplified and ultimately results in their dysfunction and death.
Why it matters
This review discusses how basal forebrain cholinergic neurons and their dependence on NGF signaling may be involved in Alzheimer pathogenesis, and suggests that studying people with Down syndrome could give useful insights. It addresses current attempts to prevent and treat Alzheimer's disease but reports no new treatment results.
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Postmortem cortical pathology was left-lateralized in both FTLD-TDP (beta = -0.15, standard error [SE] = 0.05, p = 0.007) and FTLD-Tau (beta = -0.09, SE = 0.04, p = 0.015), but the degree of lateralization decreased with greater overall dementia severity before death (beta = -8.18, SE = 3.22, p = 0.015).
Why it matters
In people with primary progressive aphasia, two different proteins (TDP-43 and tau) build up mostly on the left side of the brain, and this left-sided pattern becomes less pronounced as overall dementia gets worse. The two proteins also differ in which brain regions they affect most, which may help explain different language problems, but this is an autopsy study and does not test any treatment.
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In Alzheimer's disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF Val66Met ) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNF Val66Met an important modulating factor of cognitive impairment in AD.
Why it matters
This study found that the BDNF Val66Met variant was linked to a stronger decrease in hippocampus to medial-frontal connectivity in people with Alzheimer's disease pathology. It concerns how a genetic variant modulates brain networks and does not test any treatment, cure or prevention.
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All patients underwent MRI and β-amyloid biomarker testing via 11 C-PiB or cerebrospinal fluid. 18 F-flortaucipir uptake in patients was compared to 53 β-amyloid negative normal controls using voxelwise and pre-specified region of interest approaches.
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They belong to the spectrum of neurodegenerative diseases that result in death or dysfunction of neurons with similarities to Alzheimer disease (AD) but also distinctive differences (reviewed (Canet et al., Front Cell Neurosci 12: 307, 2018)).
Why it matters
This review discusses plasma neuronal exosomes as potential blood-based biomarkers for cognitive impairment in HIV infection and Alzheimer's disease. Blood biomarkers could make diagnosis less costly and invasive, but this paper does not report a treatment, cure, or prevention.
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The microglial triggering receptor expressed on myeloid cells 2 (TREM2) signals via the activatory membrane adaptor molecule TYROBP.
Why it matters
In aged mice bred without the immune gene TREM2, the study found "decreased age-related neuronal loss in the substantia nigra and the hippocampus", and 211 genes with changed activity, "mostly downregulated and associated with complement activation and oxidative stress response pathways." This suggests TREM2 activity in the brain's immune cells may contribute to the mild neuron loss of normal aging. These are mouse findings about normal aging, not Alzheimer's disease, and do not show a treatment, cure or prevention.
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Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD).
Why it matters
In people carrying dominant Alzheimer's mutations, progranulin levels in cerebrospinal fluid rose over the course of the disease and differed from non-carriers up to 10 years before expected symptoms. This suggests progranulin could serve as an early marker of disease progression, but the study measured levels rather than testing any treatment.
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Integrative gene network approaches enable new avenues of exploration that implicate causal genes in sporadic late-onset Alzheimer's disease (LOAD) pathogenesis, thereby offering novel insights for drug-discovery programs.
Why it matters
In a mouse model of Alzheimer's-type cerebral amyloidosis, removing TYROBP/DAP12 normalized the clinical phenotype and complement molecular pathology without reducing amyloid-beta burden. This is an animal study, so it does not show that this approach treats, cures or prevents Alzheimer's in people.
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TYROBP/DAP12 forms complexes with ectodomains of immune receptors (TREM2, SIRPβ1, CR3) associated with Alzheimer's disease (AD) and is a network hub and driver in the complement subnetwork identified by multi-scale gene network studies of postmortem human AD brain.
Why it matters
In tauopathy mice, removing TYROBP improved learning and synaptic function but unexpectedly increased tau hyperphosphorylation and spread. This is animal research only and reports no treatment, cure or prevention for people.
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48/100
Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism.
Why it matters
Using a mouse model of Alzheimer's disease, this study found that cholesterol impairs autophagy-mediated clearance of amyloid beta while promoting its secretion. This is animal work and does not yet show that lowering cholesterol in people would treat or prevent the disease.
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Hyperphosphatemia has been associated with increased mortality in chronic kidney disease but the nature of such a relation in the general population is unclear.
Why it matters
This Rotterdam Study examined whether serum phosphate levels relate to all-cause and cause-specific mortality, including deaths classified as dementia, in men. It is an observational study, so it cannot show that changing phosphate levels prevents or treats dementia.
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Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair.
Why it matters
This review states that chronic inflammation in the nervous system can be particularly injurious and contributes importantly to disease processes, including in Alzheimer's disease. It offers no treatment or prevention result, only the general idea that prolonged neuroinflammation is harmful.
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Accumulating evidence suggests that many classes of DNA repeats exhibit attributes that distinguish them from other genetic variants, including the fact that they are more liable to mutation; this enables them to mediate genetic plasticity.
Why it matters
This review explains that expansions of tandem DNA repeats can cause disorders including frontotemporal dementia, and that repeat polymorphisms may also regulate gene expression and contribute to missing heritability. It is a general genetics overview and does not report any treatment, cure or prevention.
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Regional binding of 3 H-THK5117 and 3 H-THK5351 was similar, except in the temporal cortex, which showed higher 3 H-THK5117 binding.
Why it matters
This laboratory study compared how four tau PET tracers bind to brain tissue from deceased people with Alzheimer's disease, finding similar regional binding for three of them and off-target binding for some tracers in the hippocampus and putamen. It is a technical comparison of imaging tracers and does not test any treatment, cure or prevention.
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Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD).
Why it matters
This study examined where TREM2 is expressed in human brain tissue and questioned the assumption that findings from animal models apply directly to humans. It is descriptive human tissue research and does not test a treatment.
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Previous studies have prioritized trait-relevant cell types by looking for an enrichment of genome-wide association study (GWAS) signal within functional regions.
Why it matters
Using a new method called RolyPoly, the researchers found a significant association between microglia and late-onset Alzheimer's disease. Genes differentially expressed in the prefrontal cortex of people with Alzheimer's disease were significantly enriched with genes ranked highly by the method.
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48/100
There was an age-related increase in both 18 F-AV-1451 binding in the basal ganglia and R 2 * values in the putamen in both the controls and the Alzheimer disease/mild cognitive impairment patients. 18 F-AV-1451 binding in the basal ganglia increased with R 2 * values.
Why it matters
This study shows that a commonly used tau PET tracer binds to iron in the basal ganglia as people age, which is not related to Alzheimer's disease itself. This means some tracer signal in that brain region may not reflect Alzheimer's pathology, and more autopsy work is needed to understand this.
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48/100
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions.
Why it matters
This review describes how activated microglia and neuroinflammation occur in Alzheimer's disease, Parkinson's disease and glaucoma, and how pro-inflammatory cytokines can worsen neuronal damage. It is a summary of inflammatory mechanisms and does not report a treatment, cure or prevention.
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However, the brain plasticity associated with these proposed benefits of combined therapy has not yet been investigated in elderly subjects.
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Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced.
Why it matters
In aged mice, voluntary exercise was reported to promote glymphatic clearance of amyloid beta and reduce activation of astrocytes and microglia. This is animal research and does not establish that exercise treats or prevents Alzheimer's disease in people.
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As the primary immune response cell in the central nervous system, microglia constantly monitor the microenvironment and respond rapidly to stress, infection, and injury, making them important modulators of neuroinflammatory responses.
Why it matters
This laboratory study used mouse microglia and astrocytes to examine how microglia amplify astrocyte inflammation in manganese toxicity. It is early cell research and does not test any Alzheimer's treatment or prevention.
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.
- Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease
- rs140926439 Variant in the Fibronectin FN1 Gene Lowers Risk of Alzheimer Disease in APOEε4 Carriers in the UK Biobank Cohort
- The novel sphingolipids cP1P and P1P attenuate neuroinflammation and enhance S1PR1/Akt/mTOR signaling to mitigate cognitive decline in an Alzheimer’s disease mouse model
- Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study
- S100beta protein expression: gender- and age-related daily changes
- The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome
- Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation
- Diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration
- The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease
- TREM2 in Alzheimer's Disease: Microglial Survival and Energy Metabolism