Each study has a usefulness score out of 100 (rubric version 4.0). Tap a score to see what makes it up.
Download bibliography of all 4,766 studies, highest score first: BibTeX (.bib) · RIS (.ris)
Highest usefulness score first. Studies without a score come last.
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Glutamate released by activated microglia induces excitoneurotoxicity and may contribute to neuronal damage in neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis.
Why it matters
This laboratory study reports that TNF-alpha released from activated microglia can trigger glutamate release and neurotoxicity. It is a cell-level mechanism study and reports no treatment, cure or prevention for Alzheimer's disease.
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The deficits characteristic of Alzheimer's disease (AD) are believed to result, at least in part, from the neurotoxic effects of beta-amyloid peptides, a set of 39-43 amino acid fragments derived proteolytically from beta-amyloid precursor protein (APP).
Why it matters
In a mouse model of Alzheimer's-like disease, removing a specific cleavage site on the amyloid precursor protein prevented synaptic loss, brain atrophy and behavioral deficits even though amyloid plaques still formed. This suggests that a fragment other than beta-amyloid may contribute to the disease, but the work was done only in mice and does not yet show a treatment for people.
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Since previous investigations reported improvements in cognition of patients with dementia after acetyl-L-carnitine therapy and since there is an increased risk for persons with Down syndrome to develop Alzheimer disease, this study was designed to investigate the effect of acetyl-L-carnitine administration on neurological, intellectual, and social functions in adults with Down syndrome.
Why it matters
In this double-blind study of 40 adults with Down syndrome, acetyl-L-carnitine given for six months did not enhance central nervous system functions and did not benefit the participants. The study found no cognitive or functional benefit from this treatment.
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49/100
Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.
Why it matters
In 60 non-demented people, carriers of the APOE epsilon 4 allele showed reduced white matter integrity in the posterior corpus callosum and medial temporal lobe compared with non-carriers. The authors note the mechanism is unknown but suggest that genetic risk for Alzheimer's disease is associated with microscopic brain changes well before dementia onset.
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Quantitative magnetic resonance imaging and neuropsychological evaluations were performed in 1820 dementia- and stroke-free participants from the Framingham Offspring Cohort.
Why it matters
In 1,820 adults from the Framingham Offspring Cohort without dementia or stroke, those with large volumes of white matter hyperintensities (an MRI finding) scored worse on visuospatial memory and organization, visual scanning and motor speed, and new learning than those with little or none. Verbal memory did not differ. This compares groups of people, so it shows a link, not that these brain changes cause thinking problems, and it tested no treatment.
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Microglia are innate immune cells of myeloid origin that take up residence in the central nervous system (CNS) during embryogenesis.
Why it matters
This review proposes that microglia do not have just one activated state but exist along a continuum, from a phagocytic innate response to an antigen-presenting adaptive response. It does not report any treatment, cure or prevention result, so its relevance to patients is currently conceptual rather than clinical.
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Apolipoprotein E (apoE) genotype has a major influence on the risk for Alzheimer disease (AD).
Why it matters
In PDAPP mice, deleting the lipid transporter gene Abca1 lowered brain apoE levels but, contrary to the researchers' prediction, led to significantly more hippocampal amyloid-beta and more frequent cerebral amyloid angiopathy at 12 months. The leftover apoE was poorly lipidated, less soluble and deposited alongside amyloid plaques, which led the authors to suggest that poorly lipidated apoE "is strongly amyloidogenic in vivo". This is a mouse genetics study with no human or treatment outcome; it points to apoE's lipid state, not just its amount, as relevant to amyloid build-up.
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Deficiency in docosahexaenoic acid (DHA), a brain-essential omega-3 fatty acid, is associated with cognitive decline.
Why it matters
In cytokine-stressed human neural cells, DHA reduced amyloid-beta secretion and formed NPD1, and DHA and NPD1 were reduced in the hippocampus of Alzheimer's disease brains. These findings are from cell and tissue studies, so it is not yet known whether DHA or NPD1 could be used to treat or prevent Alzheimer's disease in people.
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Abnormal folding of alpha-synuclein (alpha-syn) is thought to lead to neurodegeneration and the characteristic symptoms of Lewy body disease (LBD).
Why it matters
In a mouse model of Lewy body disease, vaccination with human alpha-synuclein reduced accumulation of aggregated alpha-synuclein and was associated with reduced neurodegeneration in mice that produced high-affinity antibodies. This is an early animal study suggesting a possible approach for Lewy body disease, not a proven treatment for Alzheimer's disease.
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Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-Hakola disease, is a presenile dementia associated with loss of myelin, basal ganglia calcification, and bone cysts.
Why it matters
This paper compares neurologic and neuroradiologic follow-up data from six patients with PLOSL (Nasu-Hakola disease) carrying TREM2 mutations with cases caused by defective DAP12 genes, and reviews known mutations in these two genes. It concerns this rare inherited dementia and does not report a treatment, cure or prevention for Alzheimer's disease.
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49/100
Transgenic mice overexpressing the P301L mutant human tau protein exhibit an accumulation of hyperphosphorylated tau and develop neurofibrillary tangles.
Why it matters
In P301L tau transgenic mice, this work found mitochondrial dysfunction, reduced complex V levels, impaired respiration and ATP synthesis, and greater vulnerability to beta-amyloid. It is animal research, so it does not yet show any treatment, cure or prevention for Alzheimer's disease.
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BACE is a transmembrane protease with beta-secretase activity that cleaves the amyloid precursor protein (APP).
Why it matters
In laboratory experiments using protein-proximity imaging (FRET/FLIM) and co-immunoprecipitation, this study found that the light chain of the receptor LRP "interacts with BACE on the cell surface in association with lipid rafts," and reports LRP as a new substrate of BACE1, the enzyme that starts amyloid-beta production from APP. This means BACE1 acts on more than APP. The study does not test any treatment or measure any effect on Alzheimer's disease in people.
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Neuritic plaques are a defining feature of Alzheimer disease (AD) pathology.
Why it matters
In a mouse model of Alzheimer-like pathology, clearing amyloid deposits with an anti-amyloid antibody reduced the number and size of damaged neurites within three days, suggesting this damage is partly reversible. This is an animal study and does not show any treatment, cure, or prevention in people.
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HIV-associated dementia (HAD) is an important complication of the central nervous system in patients who are infected with HIV-1.
Why it matters
This review discusses HIV-associated dementia, noting that its incidence fell with highly active antiretroviral therapy but that a milder cognitive and motor disorder remains a potential problem. It concerns HIV-associated dementia and does not address treating, curing, or preventing Alzheimer's disease.
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49/100
Tau protein is the major component of the intraneuronal filamentous inclusions that constitute defining neuropathological characteristics of Alzheimer's disease and other tauopathies.
Why it matters
In test-tube experiments, several phenothiazines, polyphenols, and a porphyrin inhibited heparin-induced tau filament formation and also inhibited Abeta fibril formation. This is in-vitro work only and does not show that these compounds treat or prevent Alzheimer's disease in people.
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Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia.
Why it matters
In 14 people with mild cognitive impairment, diffusion tensor imaging showed higher mean diffusivity in several white matter regions and the left hippocampus compared with controls, while fractional anisotropy did not differ. The authors suggest these measures may reflect early tissue changes, but the study was small.
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49/100
Progressive non-fluent aphasia (PNFA) is a syndrome in which patients lose the ability to communicate fluently in the context of relative preservation of single word comprehension and non-linguistic cognitive abilities.
Why it matters
In this study of 10 patients with progressive non-fluent aphasia, PET showed hypometabolism including the left anterior insula/frontal opercular region, while voxel-based morphometry revealed only one small area of atrophy. It describes brain changes in this language condition and does not test any treatment, cure, or prevention for Alzheimer's disease.
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L-Arginine is the only endogenous nitrogen-containing substrate of NO synthase (NOS), and it thus governs the production of NO during nervous system development as well as in disease states such as stroke, multiple sclerosis, Parkinson's disease, and HIV dementia.
Why it matters
This laboratory study found that limiting L-arginine blocked nitric oxide production in cytokine-stimulated astrocytes by preventing iNOS protein expression. It is cell-level research and does not show a treatment for Alzheimer's disease.
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The brain is not only immunologically active of its own accord, but also has complex peripheral immune interactions.
Why it matters
This review hypothesizes that cytokines influence cognition through diverse mechanisms and notes a growing appreciation of cytokine-mediated inflammatory processes in neurodegenerative diseases such as Alzheimer's disease and vascular dementia. It is a conceptual review and reports no treatment, cure or prevention.
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The identification of amyloid deposits in living Alzheimer disease (AD) patients is important for both early diagnosis and for monitoring the efficacy of newly developed anti-amyloid therapies.
Why it matters
In postmortem Alzheimer's brain tissue, a Congo red–derived dye called methoxy-X04 stained plaques, tangles and blood-vessel amyloid "with good specificity." In living transgenic mice, a single injection let researchers see individual plaques "within 30 to 60 min," and a radiolabelled version entered rat brain well enough that the authors call it "a viable candidate" for human PET amyloid imaging. This is lab and animal work only; it does not show the dye works in living people, and it is not a test or a treatment.
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The substantia nigra is not the induction site in the brain of the neurodegenerative process underlying Parkinson disease (PD).
Why it matters
In 30 autopsy cases with incidental Lewy body pathology, the earliest Lewy neurites and bodies appeared in non-catecholaminergic brainstem and olfactory regions before any nigral involvement. This describes where Parkinson's pathology begins and tests no treatment.
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Increasing evidence has suggested that inflammation in the brain is closely associated with the pathogenesis of several degenerative neurologic disorders, including Parkinson's disease, Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia.
Why it matters
This review describes how activated glial cells produce proinflammatory and neurotoxic factors including nitric oxide, and attributes excessive nitric oxide production to participation in neurodegeneration. It reports no treatment or prevention result for Alzheimer's disease.
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Traumatic brain injury (TBI) increases susceptibility to Alzheimer's disease (AD), but it is not known how TBI contributes to the onset or progression of this common late life dementia.
Why it matters
In a transgenic mouse model of Alzheimer amyloidosis, repetitive mild traumatic brain injury increased amyloid beta levels, deposition, lipid peroxidation, and cognitive impairment. These are animal findings, so they do not establish that preventing head injury prevents Alzheimer's disease in people.
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49/100
Pronounced disruptions of distributed cooperative activity in schizophrenia were found.
Why it matters
In this small imaging study, a pattern of brain activity separated all schizophrenia patient scans from comparison scans and was validated in a new cohort. It concerns schizophrenia and a possible trait marker, not Alzheimer's disease treatment, cure or prevention.
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Apolipoprotein (apo) E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges.
Why it matters
This study examined the relationship between APOE genotype, a gene variant linked to dementia and high cholesterol, and cardiovascular disease in 3,413 participants of the Framingham Offspring Study. It explored shared risk factors between heart disease and dementia but did not test any treatment.
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.
- Immune and metabolic effects of African heritage diets versus Western diets in men: a randomized controlled trial
- P2RX7 modulates the function of human microglia-like cells and mediates the association of IL18 with Alzheimer's disease traits
- Age-Related Prevalence of Abnormal Plasma p-Tau217 Across Racial Ethnic Groups in the Health and Aging Brain Study-Health Disparities
- Transcriptome and metabolome analysis of crGART, a novel cell model of de novo purine synthesis deficiency: Alterations in CD36 expression and activity
- Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)
- No robust add-on effects of prefrontal theta–gamma tACS to cognitive training on episodic memory in non-demented older adults
- Insomnia, early and late rising are associated with small hippocampal volume and large white matter hyperintensity burden
- Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study
- Inhibition of REV-ERBs stimulates microglial amyloid-beta clearance and reduces amyloid plaque deposition in the 5XFAD mouse model of Alzheimer's disease
- New Horizons: Gonadotropin-Releasing Hormone and Cognition