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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Gliomas are the most common and aggressive type of primary adult brain tumors.
Why it matters
This study is about glioma, a type of brain tumor, not Alzheimer's disease. It found TREM2 overexpressed in glioma tissues and linked to tumor grade and survival, which does not inform Alzheimer's treatment.
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The chemokine/chemokine receptor CCL2/CCR2 axis was impaired in BDMs from AD and MCI patients, causing a deficit in cell migration.
Why it matters
In blood-derived monocytes and macrophages from people with Alzheimer's disease and mild cognitive impairment, this study found impaired CCL2/CCR2 chemotaxis and altered phagocytosis of amyloid beta fibrils. These are laboratory observations about immune cell behavior, not a demonstrated treatment or cure.
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41/100
Many insults, including trauma, ischemia, infection, inflammation, and neurodegeneration, result in irreversible damage to the central nervous system.
Why it matters
This is a review of naturally occurring antibodies as possible treatments for several neurologic diseases, including Alzheimer's disease, not a test of a treatment in patients. It notes that many approaches that work in animal models fail in humans due to lack of efficacy or toxic effects, so no treatment benefit is established here.
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Attention deficit is one of the core symptoms of the attention-deficit/hyperactivity disorder (ADHD).
Why it matters
This genetic study of attention function in adults with ADHD found no variants reaching genome-wide significance, though one suggestive signal was in the SORCS2 gene, previously linked to Alzheimer disease among other conditions. The findings are preliminary and do not directly address treating, curing, or preventing Alzheimer disease.
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Alzheimer's disease is a severe neurodegenerative disorder of the brain, pathologically characterized by extracellular beta-amyloid plaques, intraneuronal Tau inclusions, inflammation, reactive glial cells, vascular pathology and neuronal cell death.
Why it matters
In cultured brain slices from adult Alzheimer's model mice, the proteases neprilysin, insulysin, and MMP-9 degraded beta-amyloid plaques, but only at the highest concentration tested. This is an in vitro model, so it does not show that these proteases could clear plaques or improve outcomes in living patients.
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Bach1, among the genes encoded on chromosome 21, is a transcription repressor, which binds to antioxidant response elements of DNA thus inhibiting the transcription of specific genes involved in the cell stress response including heme oxygenase-1 (HO-1).
Why it matters
In brain tissue from all Down syndrome cases studied, total Bach1 protein levels were increased along with reduced induction of HO-1, and the development of Alzheimer's disease in Down syndrome was characterized by increased Bach1, increased HO-1 and increased nitration of BVR-A with reduced activity. The findings were also examined in the Ts65Dn mouse model at 3 and 15 months of age.
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Previous data demonstrate that bexarotene (Bex), retinoid X receptor (RXR) agonist, reduces soluble and insoluble amyloid-β (Aβ) in Alzheimer disease (AD)-transgenic mice either by increasing the levels of mouse apolipoprotein E (apoE) or increasing ABCA1/ABCG1-induced apoE lipoprotein association/lipidation.
Why it matters
In mice carrying the human APOE4 gene, which is the strongest genetic risk factor for Alzheimer's, short-term treatment with retinoid X receptor drugs (bexarotene or LG100268) raised the fat-carrying ("lipidated") form of apoE4 and lowered soluble amyloid in the hippocampus. The same short-term treatment raised soluble amyloid in the cortex, possibly because the drugs enlarged the liver, and a prevention schedule showed no benefit. This is mouse research only. It suggests the APOE4 problem may be too little lipidated apoE4, but it does not show that these drugs help people.
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An imbalance of tau isoforms containing either three or four microtubule-binding repeats causes frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) in families with intronic mutations in the MAPT gene.
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41/100
Adults with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by 40 years of age.
Why it matters
In autopsy brain tissue, this study found lower synaptophysin in Down syndrome with Alzheimer disease than in Down syndrome alone, and higher synaptojanin-1 in Down syndrome that rose further with Alzheimer pathology. These are tissue findings after death and do not show any treatment, cure or prevention.
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Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (Aβ) peptide with reactive microglia.
Why it matters
In a transgenic mouse model of Alzheimer disease, three months of pomegranate extract in drinking water decreased the path length to escape in a maze test compared with the mice's own starting performance. This is animal research only, so it does not show that pomegranate extract treats or prevents Alzheimer disease in people.
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Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning.
Why it matters
This early work used blood proteins to build scores that predicted performance on specific neuropsychological tests in a sample of 395 people. The authors describe it as proof of concept for a new approach they call 'molecular neuropsychology,' not a ready test for patients.
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Prior work has shown that iron interacts with hyperphosphorylated tau, which contributes to the formation of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD), whereas iron chelator desferrioxamine (DFO) slows down the clinical progression of the cognitive decline associated with this disease.
Why it matters
This study found that high-dose iron increased tau phosphorylation in the brains of APP and presenilin 1 double transgenic mice, and that intranasal deferoxamine inhibited this effect. It is animal research and does not test whether deferoxamine treats or prevents Alzheimer's disease in people.
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Alzheimer disease (AD) is neuropathologically characterized by the formation of senile plaques from amyloid-β (Aβ) and neurofibrillary tangles composed of phosphorylated Tau.
Why it matters
In a cell coculture system, naturally secreted amyloid-beta at physiologically relevant levels induced hyperphosphorylation of Tau, and this was modulated by insulin-dependent Akt-GSK3beta signaling. This is laboratory cell work, so it does not yet show whether targeting this pathway can treat or prevent Alzheimer's disease in people.
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Microglia sense intact or lesioned cells of the central nervous system (CNS) and respond accordingly.
Why it matters
This paper describes how microglia use activating receptors such as TREM2 and CR3 to trigger immune responses, balanced by inhibitory receptors. It is a basic science review of how these receptors work, not a test of any treatment, prevention or cure in patients.
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Methylation reactions linked to homocysteine in the one-carbon metabolism are increasingly elicited in Alzheimer's disease, although the association of hyperhomocysteinemia and of low B vitamin levels with the disease is still debated.
Why it matters
In mice kept on a B vitamin deficient diet, S-adenosylmethionine supplementation was tested for effects on Alzheimer-like features. This is an animal study and does not show any treatment, cure, or prevention for Alzheimer's disease in humans.
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Down syndrome (DS) or trisomy 21 is the genetic disease with highest prevalence displaying phenotypic features that both include neurologic deficiencies and a number of clinical outcomes.
Why it matters
This review describes how oxidative stress and mitochondrial dysfunction are features of Down syndrome, related to overexpression of SOD-1 and a proinflammatory state. It discusses mechanisms only and reports no treatment, cure, or prevention for Alzheimer's disease.
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The amyloid precursor protein (APP) plays a key role in the pathogenesis of Alzheimer's disease (AD), as proteolytical cleavage of APP gives rise to the β-amyloid peptide which is deposited in the brains of Alzheimer patients.
Why it matters
This review summarizes evidence from mouse models that amyloid precursor protein and its relatives APLP1 and APLP2 have roles in nervous system development and synapse function. It discusses possible contributions to Alzheimer's disease but does not test any treatment, cure, or prevention.
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Murine transgenic models of Alzheimer's disease (Tg-AD) have been useful to analyze the contribution of β-amyloid precursor protein (βAPP), Aβ42 peptide deposition, and the proinflammatory mechanisms that characterize Alzheimer-type neuropathology.
Why it matters
In several transgenic mouse models of Alzheimer's disease, aged symptomatic 5xFAD mice showed the highest retinal amyloid-beta 42 and the lowest complement factor H. This is animal work and does not establish a treatment, cure or prevention for people.
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Endocytic system dysfunction is one of the earliest disturbances that occur in Alzheimer's disease (AD), and may underlie the selective vulnerability of cholinergic basal forebrain (CBF) neurons during the progression of dementia.
Why it matters
This study examined postmortem brain tissue and found that certain rab GTPases were upregulated in cholinergic basal forebrain neurons in people with mild cognitive impairment and Alzheimer's disease. The findings support the idea that endosomal pathology may contribute to neurodegeneration, but no treatment is tested.
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β-Amyloid (Aβ), a peptide generated from the amyloid precursor protein, is widely believed to underlie the pathophysiology of Alzheimer disease (AD).
Why it matters
This laboratory study found that soluble amyloid-beta oligomers disrupt membrane trafficking of AMPA receptors, contributing to early synapse dysfunction. It describes a mechanism of synaptic damage and does not test any treatment, cure, or prevention.
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The first reports of disorders that in terms of cognitive and behavioral symptoms resemble frontotemporal dementia (FTD) and in terms of motor symptoms resemble amyotrophic lateral sclerosis (ALS) bring us back to the second half of the 1800s. Over the last 150 years, and especially in the last two decades, there has been growing evidence that FTD signs can be seen in patients primarily diagnosed with ALS, implying clinical overlap among these two disorders.
Why it matters
This review describes the clinical and pathological overlap between frontotemporal dementia and amyotrophic lateral sclerosis and the genes involved. It is a summary of disease biology and does not test any treatment or cure.
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In conclusion the analysis of oxysterols in plasma and CSF seems to contribute to investigate the role of cholesterol metabolism in pathogenesis of neurodegeneration and is helpful in the study of patients affected by neurodegenerative diseases.
Why it matters
This paper concludes that measuring oxysterols in plasma and cerebrospinal fluid may help investigate the role of cholesterol metabolism in neurodegeneration and may be helpful in studying patients with neurodegenerative diseases. It concerns a possible biomarker, not a treatment, cure, or prevention for Alzheimer's disease.
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The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging.
Why it matters
In brains from 4 women with Down syndrome and 6 controls, the Down syndrome brains had about 40% fewer neocortical neurons and fewer glial cells, while basal ganglia neuron numbers were the same. The authors conclude that the neurodegenerative outcome in Down syndrome differs from common Alzheimer's disease, and this small post-mortem study does not test treatment.
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Vitamin D and vitamin D receptor (VDR) have been postulated as environmental and genetic factors in neurodegeneration disorders including multiple sclerosis (MS), Alzheimer disease (AD), and recently Parkinson disease (PD).
Why it matters
This genetic study found that variants in the vitamin D receptor gene were associated with Parkinson disease risk and age of onset, and some of these variants had also been linked to Alzheimer disease in other studies. It suggests vitamin D may play a role in these diseases but does not show that vitamin D treatment helps patients.
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Our findings suggest that microglial activation and the production of proinflammatory mediators by phospho-tau-positive neurons and glial cells may differentially contribute to neuronal death and disease progression in neurodegenerative tauopathies.
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.
- Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity
- TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy
- White matter hyperintensities: relationship to amyloid and tau burden
- Higher neighborhood deprivation is associated with accelerated disease progression in behavioral‐variant frontotemporal degeneration
- Red cell superoxide dismutase, glutathione peroxidase and catalase in Down syndrome patients with and without manifestations of Alzheimer disease
- DAP12 Stabilizes the C-terminal Fragment of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) and Protects against LPS-induced Pro-inflammatory Response
- Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis
- Novel Dual Mechanism GRT-X Agonist Acting on Kv7 Potassium Channel/Translocator Protein Receptor Prevents Motoneuron Degeneration Following Exposure to Mouse and Human Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Astrocyte-Conditioned Media
- Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis
- Neuroimaging standards for research into small vessel disease—advances since 2013