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.
-
Transactivation-responsive DNA-binding protein 43 (TDP-43) is a component of pathological inclusions in amyotrophic lateral sclerosis and several forms of sporadic and familial frontotemporal lobar degeneration.
Why it matters
This laboratory analysis found TDP-43 protein together with huntingtin in brain inclusions of people with Huntington disease, a condition different from Alzheimer's. It offers no treatment, cure or prevention for Alzheimer's disease.
-
MicroRNAs (miRNAs) are key regulatory RNAs known to repress mRNA translation through recognition of specific binding sites located mainly in their 3'-untranslated region (UTR).
Why it matters
Two microRNAs, miR-298 and miR-328, were found to regulate expression of mouse BACE1, and a loss of the normal relationship between BACE1 mRNA and protein was seen in a mouse model of Alzheimer's disease. This is laboratory and animal work, so it does not yet show a treatment for people.
-
Since the discovery of the amyloid precursor protein (APP) in 1987, extensive research has been conducted analyzing the APP-derived beta-amyloid (Abeta) which is found in massive quantities in senile plaques of Alzheimer disease (AD) patients.
Why it matters
This review discusses the amyloid precursor protein intracellular domain (AICD) as a possible modulator of gene expression, apoptosis and cytoskeletal dynamics, while noting it is still unclear whether beta-amyloid toxicity is an initial cause or a late event in Alzheimer's disease. It is a summary of possible mechanisms and does not report a treatment that works in patients.
-
Recent findings suggest that hypercholesterolemia may contribute to the onset of Alzheimer's disease-like dementia but the underlying mechanisms remain unknown.
Why it matters
In mice fed a high fat/cholesterol diet, memory loss was found to correlate with neuroinflammatory changes and altered amyloid precursor protein processing. This is animal work, so it does not show that lowering cholesterol in people prevents or treats Alzheimer's disease.
-
Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive disorder, caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of the glycosaminoglycan heparan sulfate.
Why it matters
This review describes Sanfilippo syndrome, a rare inherited disorder in which a buildup of heparan sulfate leads to progressive mental deterioration and severe dementia, with patients usually dying in the second or third decade of life. It is about a different, rare disease and does not address treating, curing, or preventing Alzheimer's disease.
-
These data are evidence of a gene x environment interaction for cognitive aging.
Why it matters
In this follow-up study of people born in 1936, higher total n-3 polyunsaturated fatty acid content in red blood cell membranes was associated with better cognition at about age 64 and less decline to about age 68. However, these cognitive benefits were significant only in people without the APOE epsilon4 allele, so the findings do not show that n-3 fatty acids prevent Alzheimer's disease in everyone.
-
Copper and zinc play important roles in Alzheimer disease pathology with recent reports describing potential therapeutics based on modulation of metal bioavailability.
Why it matters
This cell study found that selective intracellular release of copper and zinc from bis(thiosemicarbazonato) complexes reduced levels of amyloid-beta peptide in cells overexpressing amyloid precursor protein. It is early laboratory research and does not show a treatment or prevention for Alzheimer's disease.
-
45/100
Synaptic integrity is now recognized as a central component of Alzheimer's disease.
Why it matters
This study found that people with mild cognitive impairment had increased density of glutamatergic presynaptic boutons in the brain, which then decreased with disease progression. The findings describe a structural change in the brain during mild cognitive impairment and do not test any treatment or prevention.
-
These findings support evidence of genetic control of brain volume even in adults, particularly of hippocampal and neocortical volume and of cortical volumetric reductions being familial, but do not support measures of subcortical volumes per se as representing intermediate biologic phenotypes.
-
Our findings confirm and extend previous voxel-based morphometry analyses in ill subjects with schizophrenia.
-
45/100
The amino acid sequence of amyloid precursor protein (APP) is highly conserved, and age-related A beta aggregates have been described in a variety of vertebrate animals, with the notable exception of mice and rats.
Why it matters
In these transgenic mice, neither overexpressing mouse APP alone nor together with mutant PS1 caused Alzheimer-type amyloid pathology by 24 months of age. This is an animal study and does not show any treatment, cure, or prevention for Alzheimer's disease in humans.
-
45/100
Mutations in presenilins are responsible for approximately 40% of all early-onset familial Alzheimer disease (FAD) cases in which a genetic cause has been identified.
Why it matters
Using lipid bilayer assays and calcium imaging in cells lacking presenilin, this study found that familial Alzheimer's disease-linked mutations disrupt the ability of presenilin 1 to act as a passive calcium leak channel in the endoplasmic reticulum. This is a laboratory finding about a possible disease mechanism and does not establish a treatment or cure.
-
Amyloid precursor protein (APP) facilitates synapse formation in the developing brain, while beta-amyloid (Abeta) accumulation, which is associated with Alzheimer disease, results in synaptic loss and impaired neurotransmission.
Why it matters
This laboratory work showed that FMRP binds to APP mRNA and that mGluR5 stimulation increases APP translation in wild-type but not fmr-1 knockout samples. It is early, cell-based research and does not test any treatment or prevention for Alzheimer's disease.
-
Microglia constitute the primary resident immune surveillance cell in the brain and are thought to play a significant role in the pathogenesis of several neurodegenerative disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease and HIV-associated dementia.
Why it matters
This review discusses using PET imaging with ligands of the peripheral benzodiazepine receptor, now called translocator protein 18kDa, to detect activated microglia in living patients. It is about a possible way to measure neuroinflammation and does not report any treatment, cure or prevention of Alzheimer's disease.
-
Alzheimer's disease is the most common cause of dementia in the elderly, and manifests as progressive cognitive decline and profound neuronal loss.
Why it matters
This review describes how activated microglia around amyloid plaques produce proinflammatory molecules and that the microglial NADPH oxidase complex is a source of oxidative stress. It is a summary of mechanisms, not a clinical trial, so it offers no confirmed treatment, cure or prevention for Alzheimer's disease.
-
Neuropathologic examination of 3 patients with Alzheimer disease in the Elan Pharmaceuticals trial using antibodies specific for different Abeta species showed in one case, 4 months after the immunization, evidence of a stage of active plaque clearance with "moth-eaten" plaques and abundant Abeta phagocytosis by microglia.
Why it matters
Brain examination of 3 people with Alzheimer's from the Elan Abeta42 immunization trial found plaque-free areas after immunization (69% and 86% of the temporal cortex in two cases, 1 to 2 years later). Although most antibodies made by the immunization bind one end of Abeta (the intact N-terminus), the study reports that all major forms (Abeta40, Abeta42 and N-terminus truncated Abeta) were cleared. Tau tangles, neuropil threads and amyloid in blood vessel walls remained, and this 3-person post-mortem series reports tissue changes only, not any improvement in symptoms.
-
The expression of the purinergic receptor subtype P2X(7)R, a nonselective cationic channel activated by high levels of adenosine triphosphate (ATP), has been studied in adult microglia obtained from Alzheimer disease (AD) and nondemented (ND) brains, in fetal human microglia exposed to Abeta(1-42) peptide and in vivo in Abeta(1-42)-injected rat hippocampus.
Why it matters
Microglia from Alzheimer's disease brains and from amyloid-beta-treated cells showed increased P2X7 receptor expression, and similar findings appeared in amyloid-beta-injected rat hippocampus. This describes an association in tissue and animals, not a treatment or cure.
-
Two common disorders of the elderly are heart failure and Alzheimer disease (AD).
Why it matters
This work links mutations in the presenilin genes PSEN1 and PSEN2, already known to cause familial Alzheimer's disease, to dilated cardiomyopathy and heart failure. It suggests these genes may be relevant to heart disease as well as Alzheimer's, but does not report any treatment, cure or prevention for Alzheimer's itself.
-
HIV infects tissue macrophages and brain microglia, which express lower levels of CD4 and CCR5 than CD4+ T cells in peripheral blood.
-
The low density lipoprotein receptor-related protein (LRP) is highly expressed in the brain and has been shown to alter the metabolism of amyloid precursor protein and amyloid-beta peptide (Abeta) in vitro.
Why it matters
In mice, higher levels of the receptor LRP increased accumulation of amyloid-beta42 inside neurons, and mice lacking apolipoprotein E had much less of this accumulation. These are animal and cell findings, so they suggest a possible mechanism but do not show a treatment for people.
-
45/100
LR11 is an ApoE receptor that is enriched in the brain.
Why it matters
LR11 protein was reduced in sporadic Alzheimer's disease but not in familial Alzheimer's disease or in a mouse model of amyloid buildup. This suggests LR11 loss is not caused by amyloid accumulation and may be specific to the sporadic form of the disease.
-
Telomere length is a prognostic marker for poststroke cognitive decline, dementia, and death.
Why it matters
Among non-demented stroke survivors, longer telomeres at baseline were linked to lower risk of death and dementia and less decline in Mini-Mental State Examination scores. This identifies telomere length as a prognostic marker after stroke, not a treatment or cure.
-
Adult proliferation and hippocampal neurogenesis are stimulated by injury.
Why it matters
In presenile Alzheimer's disease cases, increased proliferating cells in the hippocampus were mainly due to glial and vasculature-associated changes, and the study found no indications for altered dentate gyrus neurogenesis. It reports no treatment, cure or prevention.
-
Our findings show an association between low circulating levels of one of the most important components of the human antioxidant system and the presence of frailty.
-
Oxidative damage is a feature of many age-related neurodegenerative diseases, including Alzheimer's disease (AD). 4-Hydroxy-2-nonenal (HNE) is a highly reactive product of the free radical-mediated lipid peroxidation of unsaturated lipids, particularly arachidonic acid, in cellular membranes.
Why it matters
This study found elevated levels of a lipid peroxidation product, HNE, in the hippocampus and inferior parietal lobule of people with MCI compared with controls. It suggests that preventing lipid peroxidation at the MCI stage might be a future strategy, but no treatment was tested.
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 and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes
- Early and Longitudinal Microglial Activation but Not Amyloid Accumulation Predicts Cognitive Outcome in PS2APP Mice
- Spatial Transcriptomics: Biotechnologies, Computational Tools, and Neuroscience Applications
- Role of phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) in intracellular amyloid precursor protein (APP) processing and amyloid plaque pathogenesis
- Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints
- The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin
- Cytokine actions in the central nervous system
- Influence of co-pathology on CSF and plasma synaptic markers SNAP25 and VAMP2 in Alzheimer’s disease and Parkinson’s disease
- Plasma proteomics for cognitive decline and dementia—A Southeast Asian cohort study
- MCC950 suppresses NLRP3-dependent neuroinflammation and ameliorates cognitive decline in a rat model of cerebral small vessel disease