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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46/100
Recent genetic studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathophysiology of Alzheimer's disease (AD).
Why it matters
This review discusses optical imaging evidence that microglia form a barrier encapsulating amyloid deposits, which modulates plaque compaction and reduces neurotoxicity. It describes a possible neuroprotective function of microglia but the mechanisms by which microglia alter Alzheimer's disease remain poorly understood.
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46/100
ApoE4-CLEAR interactions may account for suppressed autophagy in APOE ɛ4/ɛ4 carriers and, in this way, contribute to earlier AD onset.
Why it matters
This study found that three autophagy-related gene transcripts were lower in Alzheimer's brains from APOE ε4/ε4 carriers compared to ε3/ε3 carriers, and computational modeling predicted that apoE4 binds to CLEAR DNA motifs and competes with TFEB. The findings suggest a mechanism for suppressed autophagy in APOE ε4 carriers, but no treatment is tested.
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TREM2 plays a critical role in the alleviation of Alzheimer's disease by promoting Aβ phagocytosis by microglia, but the detailed molecular mechanism underlying TREM2-induced direct phagocytic activity of Aβ remains to be revealed.
Why it matters
In mice, extra TREM2 went with better learning and memory in old age and losing TREM2 went with worse, and microglia from TREM2-knockout mice took up "significantly reduced" amounts of amyloid-beta. Levels of CD36, a receptor on microglia, and of C/EBPα, a protein that switches CD36 on, rose and fell along with TREM2, which suggests one possible route by which TREM2 helps microglia take up amyloid. This is mouse and cell work with no human data, so it does not show that targeting TREM2, CD36 or C/EBPα would treat Alzheimer's in people.
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Perivascular macrophages (PVM) are a distinct population of resident brain macrophages characterized by a close association with the cerebral vasculature.
Why it matters
This review describes perivascular macrophages, a distinct brain macrophage population, and notes their involvement in several conditions including Alzheimer disease pathology. It is a descriptive overview and does not report any treatment, cure or prevention for Alzheimer's disease.
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46/100
We examined the effect of chronic high fat diet (HFD) on amyloid deposition and cognition of 12-months old APP23 mice, and correlated the phenotype to brain transcriptome and lipidome.
Why it matters
In Alzheimer's model mice, a high fat diet increased amyloid plaques, worsened cognitive performance and raised expression of immune genes including Trem2. This is early animal work suggesting diet may affect Alzheimer's-like pathology, but it does not show that any treatment prevents or cures Alzheimer's disease in people.
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Although post-ischemic inflammation induced by the innate immune response is considered an essential step in the progression of cerebral ischemia injury, the role of triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of ischemic stroke remains to be elucidated.
Why it matters
In mice and cultured microglia, TREM2 levels rose after stroke-like injury, and changing TREM2 levels affected the injury response. This concerns cerebral ischemia in mice, not Alzheimer's disease treatment or prevention.
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This study assesses whether C-terminal fragments (CTF) of the amyloid precursor protein (APP) are present in cerebrospinal fluid (CSF) and their potential as biomarkers for Alzheimer's disease (AD).
Why it matters
A fragment of the amyloid precursor protein was found at higher levels in spinal fluid from people with inherited Alzheimer disease, demented Down syndrome individuals, and sporadic Alzheimer disease. The authors suggest it could be a diagnostic biomarker, not a treatment or cure.
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Nasu-hakola disease (NHD) is a rare disease characterized by bone cysts and fractures, frontal lobe syndrome, and progressive presenile dementia.
Why it matters
This case report describes a 33-year-old woman with a phenotype suggestive of Nasu-Hakola disease and a novel mutation in TREM2, and reviews the literature linking rare TREM2 variants to increased risk of several neurodegenerative diseases. It is a single case report and does not report any treatment, cure, or prevention for Alzheimer's disease.
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SUVR at 60-90 min after injection gave robust quantitation of (18)F-GE180, which correlated well with distribution volume ratios calculated from the entire recording and using a white matter reference region.
Why it matters
In a mouse model of Alzheimer-like amyloid, PET showed age-dependent microglial activation along with amyloid and metabolic changes. These are animal findings and do not establish any treatment or prevention for people.
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Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam.
Why it matters
In experiments with vervets fed a cyanobacterial toxin for 140 days, the animals developed neurofibrillary tangles and sparse β-amyloid deposits, and co-administration of l-serine significantly reduced the density of tangles. This is animal research suggesting that an environmental toxin can trigger neurodegeneration and that l-serine in the diet can reduce the risk, not a proven treatment or prevention for Alzheimer's disease in people.
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Neuroinflammation is an important feature in the pathogenesis and progression of neurodegenerative diseases such as Alzheimer´s disease (AD), Parkinson´s disease (PD), frontotemporal dementia and amyotrophic lateral sclerosis.
Why it matters
This review analyzes the LPS-treated mouse model of peripherally induced neuroinflammation and neurodegeneration, used to test anti-inflammatory drugs and natural products. It is a description of an animal model and reports no proven treatment or prevention for Alzheimer's disease in people.
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Amyloid β (Aβ) damages neurons and triggers microglial inflammatory activation in the Alzheimer disease (AD) brain.
Why it matters
In transgenic mice and SH-SY5Y cells, reducing p38alpha MAPK facilitated lysosomal degradation of BACE1 and attenuated amyloid pathology. This is animal and cell-model evidence and does not demonstrate that targeting p38alpha MAPK treats or prevents Alzheimer's disease in people.
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46/100
(18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.
Why it matters
A new PET tracer called 18F-THK5351 bound selectively to neurofibrillary tangles and showed favorable properties in first-in-human PET studies in Alzheimer's disease patients. This is a tool for detecting tau pathology and does not show that any treatment based on it works.
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46/100
The differential diagnosis of Parkinson's diseases (PD) is challenging, especially in the early stages of the disease.
Why it matters
This study found differences in exosomal microRNA and other RNA molecules in cerebrospinal fluid between people with Parkinson's disease, Alzheimer's disease and healthy controls. It is about using these molecules as biomarkers to help tell these diseases apart, not about treating or preventing Alzheimer's disease.
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Proteins belonging to the 'A Disintegrin And Metalloproteinase' (ADAM) family are membrane-anchored proteases that are able to cleave the extracellular domains of several membrane-bound proteins in a process known as 'ectodomain shedding'.
Why it matters
This review notes that ADAM10 was described as the amyloid precursor protein alpha-secretase and has attracted interest as a possible drug target, but its normal functions in the brain are still not well understood. It also notes that mice lacking ADAM10 die before birth, which complicates study of the enzyme; no treatment is reported.
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Neuroinflammation is a pathological hallmark of Alzheimer's disease (AD), and microglia, the brain's resident phagocyte, are pivotal for the immune response observed in AD.
Why it matters
This review describes how microglia can be protective but may become inappropriately reactive and drive neuropathology in Alzheimer's disease. It reports that many gene variants linked to late-onset Alzheimer's relate to the immune response, endocytosis and lipid biology, but offers no treatment.
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At present, there are very few therapeutic options for patients affected by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
This review discusses aggregated TDP-43 as a promising target for developing therapies in ALS and tau-negative frontotemporal dementia, including efforts to reduce aggregation or enhance its clearance. It concerns ALS and FTD and does not provide a treatment, cure or prevention for Alzheimer's disease.
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Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system, being expressed in neurons and non-neuronal cells, where they participate in a variety of physiological responses like memory, learning, locomotion, attention, among others.
Why it matters
This review discusses the alpha7 nAChR subtype as a possible therapeutic target because of its role in neuroprotection and because oxidative stress and neuroinflammation are common in neurodegenerative diseases. It presents no tested treatment or cure for Alzheimer's disease.
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Alzheimer disease (AD) is characterized by amyloid-β accumulation, with soluble oligomers (Aβo) being the most synaptotoxic.
Why it matters
In several Alzheimer mouse models and post-mortem human brain, high molecular weight amyloid β oligomers that interact with prion protein tracked closely with memory impairment. This is animal and tissue research and does not show a treatment, cure, or prevention for people.
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The paired helical filaments (PHF) formed by the intrinsically disordered human protein tau are one of the pathological hallmarks of Alzheimer disease.
Why it matters
Using neutron scattering and molecular dynamics simulations, this laboratory study found that hydration water is more mobile around tau fibers than around monomeric tau, while water dynamics around the fiber core domain were reduced after fiber formation. This is basic in-vitro work on tau fiber formation and does not test any treatment, cure or prevention in people.
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Tauopathies are clinically, morphologically and biochemically heterogeneous neurodegenerative diseases characterized by the deposition of abnormal tau protein in the brain.
Why it matters
This review describes the different neuropathological forms of tauopathies and notes that tau gene mutations cause frontotemporal dementia and parkinsonism linked to chromosome 17. It is a classification and pathology review and does not report a treatment or cure.
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Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3-5 years after onset--a description which suggests that the clinical presentation of ALS is very homogenous.
Why it matters
This review describes the considerable variability in how ALS presents, including motor and extramotor involvement and overlap with frontotemporal dementia. It discusses implications for understanding the disease and developing therapies but reports no treatment or cure.
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Parkinson's disease is a chronic neurodegenerative disorder characterized by the motor symptoms of bradykinesia, tremor, rigidity and postural instability.
Why it matters
This review describes loss of serotonin terminals in Parkinson's disease and links it to motor and non-motor symptoms including dementia. It is about Parkinson's disease pathology and does not test any treatment, cure or prevention for Alzheimer's disease.
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46/100
Accumulation of β-amyloid (Aβ) and resultant inflammation are critical pathological features of Alzheimer disease (AD).
Why it matters
In microglia, autophagy was shown to help degrade extracellular amyloid-beta fibrils and to regulate the NLRP3 inflammasome. This is laboratory work and does not demonstrate a treatment, cure or prevention for Alzheimer's disease.
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Our data suggest that genetically-modified NSCs could provide a powerful combinatorial approach to not only enhance synaptic plasticity but to also target and modify underlying Alzheimer's disease pathology.
Why it matters
In two mouse models of Alzheimer's disease, transplanted neural stem cells engineered to release an amyloid-degrading enzyme reduced amyloid plaques and increased synaptic density. These are animal results only, and it is not known whether this approach would be safe or effective in people.
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.
- Pattern of Tau forms in CSF is altered in progressive supranuclear palsy
- Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD)
- Myeloid LXR (Liver X Receptor) Deficiency Induces Inflammatory Gene Expression in Foamy Macrophages and Accelerates Atherosclerosis
- Plasma Neurofilament Light Chain Levels Are Associated With Cortical Hypometabolism in Alzheimer Disease Signature Regions
- Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis
- Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial
- How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder
- Mechanisms of tau-induced neurodegeneration
- Limited Diagnostic Performance of Cerebrospinal Fluid Glial Fibrillary Acidic Protein in Dementia
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies