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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Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years.
Why it matters
In two Alzheimer's neuronal cell culture models, the Crocus sativus compounds trans-crocin 4 and trans-crocetin were tested for protective effects on the amyloidogenic pathway and tau misprocessing. This is early laboratory work in cells, not in people, so it does not yet show whether these compounds can treat or prevent Alzheimer's disease.
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Clinically, superimposed systemic inflammation generally has significant deleterious effects on the Alzheimer's disease (AD) progression.
Why it matters
In an Alzheimer's mouse model, giving lipopolysaccharide to mimic systemic inflammation shifted the balance of microglial TLR4 and TREM2. This is animal work on how inflammation may relate to disease progression, not evidence of a treatment, cure, or prevention.
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Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in nonmalignant pathological processes.
Why it matters
This study is about liver cancer, not Alzheimer's disease, and reports that TREM2 acts as a tumor suppressor in hepatocellular carcinoma. It reports no Alzheimer's treatment, cure or prevention.
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Aging is regarded as a major risk factor for neurodegenerative diseases.
Why it matters
This work compared existing gene expression datasets from healthy people and people with neurodegenerative diseases, including Alzheimer's, with mouse aging and cell-type data. It is an analysis of existing data and does not test any treatment, so it cannot show whether Alzheimer's can be treated, cured or prevented.
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Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors.
Why it matters
In 12-month-old APP/PS1/tau triple-transgenic mice, female mice displayed more prominent amyloid plaques, neurofibrillary tangles, and neuroinflammation than males. This is an animal study, so the sex differences found cannot be directly assumed to apply to treating or preventing Alzheimer's disease in people.
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Neuroinflammation plays a role in the aetiopathogenesis of Alzheimer's disease (AD).
Why it matters
This study found increased TREM2 expression in peripheral cells from mild cognitive impairment patients who progressed to Alzheimer's disease. It is an observational biomarker study and does not report a treatment or cure.
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Subjects with Down Syndrome (DS) have high prevalence of cerebral vascular amyloidosis, cognitive decline and dementia.
Why it matters
In this small case-control study, adults with Down syndrome had reduced cerebral vasomotor reserve compared with controls, while carotid intima-media thickness did not differ. The authors state that larger longitudinal studies are needed to confirm these findings, so no treatment or prevention conclusion can be drawn.
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Neurotrophic factors, including the members of the neurotrophin family, play important roles in the development and maintenance of the nervous system.
Why it matters
Nerve cells must carry growth-factor signals over long distances from their branches back to the cell body, and this review covers the "signaling endosome" that does that job. It reports that changes in endosome structure are present early in both Alzheimer disease and Down syndrome, and reviews data on the APP products thought to be involved and how they may change signaling. It is a review, not a trial: it reports no treatment and concludes that more studies are needed to work out what role signaling endosomes play in neurodegeneration.
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In this chapter, we provide a review of the challenges and advances in developing successful PET imaging agents for 3 major types of aggregated amyloid proteins: amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn).
Why it matters
Developing selective PET tracers for different amyloid proteins is important because many proteopathies involve more than one amyloid protein, and selective tracers could help assess each protein's relative contribution to total amyloid burden. Success for selective alpha-synuclein PET imaging agents has not been realized yet, but work is ongoing in multiple laboratories.
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Down Syndrome (DS) is the most common genetic form of intellectual disability that leads in the majority of cases to development of early-onset Alzheimer-like dementia (AD).
Why it matters
This review discusses oxidative damage and disturbed iron metabolism in Down syndrome as possible contributors to early-onset Alzheimer-like dementia, and suggests this understanding could inform future therapeutic strategies. No treatment is tested, so no therapy is established.
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Primary Progressive Aphasia (PPA) is a neurodegenerative condition characterized by insidious irreversible loss of language abilities.
Why it matters
In this sham-controlled study, people with primary progressive aphasia who performed worse at baseline showed language improvements with transcranial direct current stimulation, while those who performed better at baseline showed only a slight benefit on speech repetition. This is a small early study of symptom relief in a related condition, not a treatment, cure or prevention of Alzheimer's disease.
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42/100
Alzheimer's disease (AD) is the most common neurodegenerative disease.
Why it matters
An intranasally delivered peptide drug ameliorated cognitive decline in Alzheimer transgenic mice. This is animal research, so it does not yet show whether the approach helps people.
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Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders.
Why it matters
In a laboratory screen using human stem cell neurons with trisomy 21, avermectins increased production of shorter amyloid beta peptides at the expense of longer ones, and this effect was not due to interaction with gamma-secretase. This is early cell-based drug screening, not evidence that any treatment works in patients.
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Clusterin (CLU) is a stress-activated, ATP-independent molecular chaperone, normally secreted from cells, that is up-regulated in Alzheimer disease and in many cancers.
Why it matters
This review discusses clusterin as a possible therapeutic target, noting that changes in the CLU gene locus are highly associated with Alzheimer's disease. It reports no tested treatment, and notes that structural work needed to target clusterin has so far not been possible.
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Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability.
Why it matters
People with Down syndrome develop the same brain plaques and tangles seen in Alzheimer's, and this review argues that oxidative damage is part of the reason. It proposes that a fat-breakdown by-product called HNE sticks to brain proteins in Down syndrome and disrupts glucose use, transport inside nerve cells, protein clean-up and antioxidant defences. The authors present this as a hypothesis drawn from earlier studies; the review reports no new data and tests no treatment.
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Triggering receptor expressed on myeloid cells 2 (Trem2), an immune-modulatory receptor, is preferentially expressed in microglia of central nervous system.
Why it matters
Trem2 is a receptor found mainly on microglia, the brain's immune cells, and is thought to possibly influence Alzheimer's disease through inflammation and the clearing of debris. This study found that Trem2 is pulled into the cell by a clathrin-dependent process and returned to the surface by Vps35, part of the retromer complex, and not by the Rab11 route. It is a study of how one receptor moves within cells; it does not test Alzheimer's outcomes or any treatment.
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42/100
Neuroinflammation is common to various diseases of the central nervous system (CNS), but its imprecise definition has led to many misconceptions in research and clinical approaches.
Why it matters
This paper argues that neuroinflammation in chronic neurodegenerative conditions such as Alzheimer's disease is distinct from the inflammation seen in relapsing-remitting multiple sclerosis. It is a discussion of immune mechanisms and does not report any treatment effect.
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The hTau40(AT) mice mimic pathological hallmarks of tauopathies including a cognitive phenotype combined with pronounced neuroinflammation visible by bioluminescence.
Why it matters
A new mouse model carrying the Tau A152T mutation developed tau pathology, synapse and neuron loss, neuroinflammation and cognitive decline with age. This is a mouse model describing how a risk mutation may cause damage, not evidence of any treatment, cure or prevention in humans.
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42/100
However, specificity of this olfactory profile to DS should be considered with some caution because cognition was not evaluated in all DS participants and comparison with a control group of non-DS individuals having cognitive disabilities was lacking.
Why it matters
This study found that smell function was severely impaired in 56 people with Down syndrome compared with controls, even at relatively young ages. The authors note that cognition was not evaluated in all participants and that further study is needed, so this does not establish a treatment or prevention.
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Long-non-coding RNAs (lncRNAs), RNA molecules longer than 200 nucleotides, have been involved in several biological processes and in a growing number of diseases, controlling gene transcription, pre-mRNA processing, the transport of mature mRNAs to specific cellular compartments, the regulation of mRNA stability, protein translation and turnover.
Why it matters
This review discusses long non-coding RNAs and their potential roles in the central nervous system and neurodegenerative diseases. It is a review of biology and mechanisms, not a clinical study, so it does not show that any treatment targeting these RNAs works.
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The triggering receptor expressed on myeloid cells (TREM) 2 is a member of the immunoglobulin superfamily of receptors and mediates signaling in immune cells via engagement of its co-receptor DNAX-activating protein of 12 kDa (DAP12).
Why it matters
This review describes how mutations in TREM2 or its co-receptor DAP12 cause Nasu-Hakola disease and how a TREM2 variant is associated with increased Alzheimer's disease risk. It summarizes existing knowledge and does not test any treatment, cure, or prevention.
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Growing evidence indicates that the activation of c-Jun N-terminal kinase (JNK) is implicated in the multiple major pathological features of Alzheimer disease (AD).
Why it matters
In middle-aged transgenic Alzheimer's disease mice, systemic administration of the JNK inhibitor SP600125 was studied for effects on neuropathology and cognitive deficits. This is an animal study and does not establish any treatment, cure, or prevention for Alzheimer's disease in humans.
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Genetic alterations or pharmacological treatments affecting endocannabinoid signaling have profound effects on synaptic and neuronal properties and, under certain conditions, may improve higher brain functions.
Why it matters
In a mouse model of Down syndrome, a drug improved long-term memory and brain signaling, but short-term and working memory were unaffected. These are animal results, so it is not yet known whether this approach would help people.
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Alterations in the Wnt signaling pathway have been implicated in Alzheimer's disease; however, its role in the processing of the amyloid precursor protein remains unknown.
Why it matters
In N2a cells, activating the Wnt pathway reduced amyloid-beta levels and BACE1 activity and expression. This was a cell study, so it does not show that targeting this pathway can treat or prevent Alzheimer's disease in people.
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Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD).
Why it matters
Treating double transgenic TAPP mice, which express mutant human tau and amyloid precursor protein, with an orally available inhibitor of O-GlcNAcase prevented cognitive decline and amyloid plaque formation. This is animal work and no treatment, cure or prevention in people is reported.
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.
- Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology
- Human apoE Isoforms Differentially Regulate Brain Amyloid-β Peptide Clearance
- Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease
- CSF α-Synuclein Seed Amplification Assay in Patients With Atypical Parkinsonian Disorders
- Partial-Volume Effect Correction Improves Quantitative Analysis of 18F-Florbetaben β-Amyloid PET Scans
- Effects of Physical Exercise on Neuroinflammation, Neuroplasticity, Neurodegeneration, and Behavior: What We Can Learn From Animal Models in Clinical Settings
- A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain-derived neurotrophic factor
- The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk
- TDP‐43 and APOE: A complex interaction
- Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions