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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SorLA has been recognized as a novel sorting receptor that regulates trafficking and processing of the amyloid precursor protein (APP) and that represents a significant risk factor for sporadic Alzheimer disease.
Why it matters
The sorting receptor sorLA was shown to hold amyloid precursor protein in the trans-Golgi compartments, preventing it from entering normal processing pathways, and this depended on interactions with the adaptor proteins GGA and PACS-1. This is cell-based mechanistic research and does not demonstrate a therapy or cure.
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The aspartyl protease beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates processing of amyloid precursor protein (APP) into amyloid beta (Abeta) peptide, the major component of Alzheimer disease (AD) plaques.
Why it matters
In a mouse model of Alzheimer's disease, removing the BACE1 gene prevented amyloid-beta generation and plaque pathology, and partially reducing BACE1 also reduced synaptic deficits. This is animal research, so it supports BACE1 as a possible target but does not prove that lowering BACE1 helps people.
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High dietary cholesterol and low dietary docosahexaenoic acid (DHA) intake are risk factors for Alzheimer's disease (AD).
Why it matters
In Alzheimer-model APP/PS1 mice fed for 12 months from 6 months of age, a high-DHA (0.5%) diet increased relative cerebral blood volume on MRI without changing blood flow and reduced beta-amyloid deposited in blood vessels, while a 1% cholesterol "Typical Western Diet" increased plaque in the dentate gyrus of the hippocampus without significantly reducing blood volume. The authors conclude that long-term dietary lipid intake "can impact both brain circulation and beta-amyloid deposition." This is an animal study with no reported cognitive outcomes or effect sizes, so it does not show that DHA or diet changes Alzheimer's in people.
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All solid organs contain resident monocyte-derived cells that appear early in organogenesis and persist throughout life.
Why it matters
This study used a mouse reporter line to track where macrophages are produced and travel during organ development. It is about normal development in mice and provides no information about treating, curing or preventing Alzheimer's.
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The somatodendritic accumulation of hyperphosphorylated tau proteins is an early event preceding the appearance of neurofibrillary tangles (NFT) in Alzheimer's disease (AD) and might be necessary for their formation.
Why it matters
This study found increased levels of active GSK-3beta in the frontal cortex of Alzheimer's disease patients and that its accumulation is an early event preceding neurofibrillary tangle formation. It does not test any treatment or prevention, so it has no direct implications for treating, curing, or preventing Alzheimer's disease.
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While there is a strong evidence for neural tissue destruction mediated by adaptive autoimmune responses, it is still debated how innate immune responses contribute to neuroinflammatory and neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease.
Why it matters
This 2007 review brings together earlier work showing that loss-of-function mutations in TREM2, an immune receptor made mainly by microglia in the brain, cause Nasu-Hakola disease (PLOSL), a rare recessively inherited condition with early-onset adult dementia and bone cysts. The authors argue that microglia are "plausible candidates" for causing the brain damage in PLOSL, because microglial TREM2 helps clear tissue debris and resolve inflammation. It reports no new data and no treatment, and it does not test a link to Alzheimer's disease.
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Lewy bodies (LBs) are pathological hallmarks of Parkinson disease (PD) but also occur in Alzheimer disease (AD) and dementia of LBs.
Why it matters
In neuronal cell experiments, the Dyrk1A enzyme was found to bind and phosphorylate alpha-synuclein at Ser-87, and blocking Dyrk1A reduced this phosphorylation and aggregate formation. These are cell-based laboratory findings, and the study does not test any treatment in people or in living animals.
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MAPK-activated protein kinase 2 (MAPKAP K2 or MK2) is one of several kinases directly regulated by p38 MAPK.
Why it matters
This study found that MK2 deficiency in microglia reduced release of pro-inflammatory mediators and the resulting neurotoxicity, suggesting a role for MK2 in neuroinflammation relevant to Alzheimer's disease. It is cell and animal research and does not show a treatment or prevention for people.
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Mutations in PSEN1 and PSEN2 genes account for the majority of cases of early-onset familial Alzheimer disease.
Why it matters
This review describes how mutations in PSEN1 and PSEN2 cause early-onset familial Alzheimer's disease and how presenilins work as the catalytic subunit of gamma-secretase. It explains disease biology and does not report a treatment or cure.
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Intracellular protein misfolding/aggregation are features of many late-onset neurodegenerative diseases, called proteinopathies.
Why it matters
This review discusses how autophagy clears aggregate-prone proteins and its therapeutic implications for proteinopathies including Alzheimer's disease. It is a discussion of a possible approach and does not report a treatment or cure.
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CSD transformation is shown to be a valuable preprocessing step for PCA of ERP data, providing a unique, physiologically meaningful solution to the ubiquitous reference problem.
Why it matters
This methods paper evaluates PCA-based analysis of ERP waveforms during auditory oddball tasks to separate brain generator patterns. It concerns brain electrical measurement technique, not Alzheimer's disease, and reports nothing about treating, curing or preventing it.
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DYRK1A, dual-specificity tyrosine-regulated kinase 1A, maps to human chromosome 21 within the Down syndrome (DS) critical region.
Why it matters
This study found altered Dyrk1A expression in neurons in Alzheimer disease, Down syndrome and Pick disease, and in a transgenic mouse model, but mice over-expressing Dyrk1A did not show increased tau phosphorylation at Thr212. It describes a possible disease association and reports no treatment or cure.
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These results provide new evidence that TREM2 regulates OC function independent of its effects on multinucleated OC differentiation.
Why it matters
In mice, TREM2 was found to regulate osteoclast function, and mutations in TREM2 or DAP12 are linked to a human bone disorder. This concerns bone biology, not Alzheimer's disease treatment or prevention.
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Cerebral vascular amyloid beta-protein (Abeta) deposition, also known as cerebral amyloid angiopathy, is a common pathological feature of Alzheimer's disease.
Why it matters
This study used transgenic mice expressing human mutant amyloid beta precursor protein to show that amyloid deposits in brain blood vessels cause vascular degeneration and neuroinflammation. It is an animal study and does not test a treatment or prevention for Alzheimer's disease in humans.
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Imprinted genes are epigenetically modified genes whose expression is determined according to their parent of origin.
Why it matters
This work used a statistical model in mice to predict potentially imprinted genes, including some put forward as candidate genes for conditions where parent-of-origin effects are involved, such as Alzheimer disease. It is a prediction study in mice and does not show that these genes cause or can be used to treat Alzheimer disease.
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Neuroinflammation has an established link with AIDS-related dementia but has not been investigated in the post-highly active anti-retroviral therapy (HAART) era.
Why it matters
This autopsy study found that even in HIV patients well treated with anti-retroviral therapy, there was a high level of microglial and macrophage activation in the brain comparable to pre-treatment levels. This concerns HIV-related brain disease, not Alzheimer's disease, and does not provide evidence about treating, curing, or preventing Alzheimer's.
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The use of statins, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that block the synthesis of mevalonate (and downstream products such as cholesterol and nonsterol isoprenoids), as a therapy for Alzheimer disease is currently the subject of intense debate.
Why it matters
This laboratory study found that statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide through an isoprenoid-dependent mechanism. This complicates the idea that statins protect against Alzheimer's disease, but it is cell-based work and does not establish what happens in patients.
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gamma-Secretase, which is responsible for the intramembranous cleavage of Alzheimer beta-amyloid precursor protein and the signaling receptor Notch, is a multiprotein complex consisting of at least four components: presenilin (PS); nicastrin (Nct); APH-1 (anterior pharynx-defective-1); and presenilin enhancer-2 (PEN-2).
Why it matters
This laboratory study shows that nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. It is basic cell biology and does not test or establish a treatment, cure or prevention for Alzheimer's disease.
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Recent studies suggest that excitotoxicity may contribute to neuronal damage in neurodegenerative diseases including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis.
Why it matters
This laboratory work describes neuritic beading induced by activated microglia as an early feature of neuronal dysfunction toward neuronal death, through inhibition of mitochondrial respiration and axonal transport. It provides no treatment, cure or prevention for Alzheimer's disease.
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44/100
Because NAA is considered a marker of neuronal integrity, reduced medial temporal and parietal lobe NAA could be an early indication of dementia-related pathology in elderly individuals.
Why it matters
Cognitively impaired but nondemented patients had reduced medial temporal lobe N-acetylaspartate and reduced hippocampal and neocortical gray matter volumes compared with controls. The authors suggest these may be early indications of dementia-related pathology in people at high risk, but this is not a treatment, cure or prevention for Alzheimer's disease.
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Few diseases are characterized by high homocysteine (HCY) and low folate and vitamin B12 blood levels.
Why it matters
In cultured cells, lowering folate and vitamin B12 reduced SAM levels, which increased presenilin 1 and BACE levels and raised amyloid beta production. This is cell-culture work linking the homocysteine cycle and DNA methylation to amyloid production, not proof that vitamin supplements prevent Alzheimer's.
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Memapsin 2 (BACE, beta-secretase) is a membrane-associated aspartic protease that initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta (A beta) and the progression of Alzheimer disease.
Why it matters
This laboratory study found that GGA proteins colocalize with memapsin 2 (BACE) in the trans-Golgi network and endosomes and help mediate its recycling pathway. It describes basic cell biology of the beta-secretase and does not test any treatment for Alzheimer's disease.
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Cyclooxygenase (COX) catalyses the first committed step in the synthesis of prostanoids, a large family of arachidonic acid metabolites comprising prostaglandins, prostacyclin, and thromboxanes, and is a major target of non-steroidal anti-inflammatory drugs (NSAIDs).
Why it matters
This review describes COX-2 as an inducible enzyme expressed in response to inflammatory signals and links its brain expression to neurodegenerative processes. It is a descriptive review and reports no treatment, cure or prevention for Alzheimer's disease.
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The neuronal lysosomal system is a major degradative pathway, induced by cell stress and closely linked to Alzheimer disease (AD) and other neurodegenerative diseases.
Why it matters
The study found that presenilin mutations causing familial early-onset Alzheimer's disease induced more severe lysosomal pathology in human brain tissue than sporadic Alzheimer's disease. It describes disease mechanisms and does not establish a treatment, cure, or prevention.
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In Alzheimer disease (AD) patients, early memory dysfunction is associated with glucose hypometabolism and neuronal loss in the hippocampus.
Why it matters
In APP/PS1 mice, amyloid-beta deposition was linked to lower glucose metabolism in the hippocampus and worse spatial memory. This supports a connection between amyloid buildup, brain energy use, and memory in a mouse model, but it does not show that any treatment changes the disease 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.
- The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44
- Hepatic danger signaling triggers TREM2+ macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation
- Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
- Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer's disease-related pathology
- Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis
- Interface between tauopathies and synucleinopathies: a tale of two proteins
- Neuroprotective Effect of TREM-2 in Aging and Alzheimer's Disease Model
- Increased CSF neurogranin concentration is specific to Alzheimer disease
- Long term high fat diet induces metabolic disorders and aggravates behavioral disorders and cognitive deficits in MAPT P301L transgenic mice
- In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson's disease