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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Patients with trisomy 21 [Down syndrome (DS)] progressively develop amyloid beta-protein (A beta) deposits and then other features of Alzheimer's disease (AD), apparently due to increased gene dosage and thus expression of the beta-amyloid precursor protein.
Why it matters
Brain tissue from 29 people with Down syndrome aged 3 to 73 showed that Aβ42 was the earliest form of amyloid beta deposited, seen as early as age 12, while Aβ40 was not detected until about age 30. Apolipoprotein E appeared after amyloid beta deposition, and the authors suggest amyloid plaque formation begins with Aβ42.
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Why it matters
Uses end-specific antibodies to visualize Abeta42(43) and Abeta40 in senile plaques, and reports evidence that an initially deposited species is Abeta42(43).
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The cause of acquired immunodeficiency syndrome (AIDS) dementia, which is a frequent late manifestation of human immunodeficiency virus (HIV) infection, is unknown but radiological and pathological studies have implicated alterations in subcortical white matter.
Why it matters
This study examined brain tissue from people with AIDS and found reduced myelin staining in some patients with dementia. It describes a pathological finding in AIDS dementia and does not test any treatment or cure.
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Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calcium-induced neuronal degeneration.
Why it matters
In postmortem brain tissue from people with Alzheimer's disease, this study found widespread activation of the calcium-activated proteinase calpain. This suggests calpain may be involved in neuronal degeneration, but it does not test any treatment.
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Microtubule-associated protein tau was purified from bovine brain microtubules by either (1) phosphocellulose chromatography, (2) heat treatment at pH 6.4, (3) heat treatment at pH 2.7, (4) heat treatment at pH 2.7 followed by extraction with perchloric acid and precipitation with glycerol, or (5) by precipitation with ammonium sulfate followed by extraction with perchloric acid.
Why it matters
Tau protein purified from bovine brain reacted with antibodies to Alzheimer paired helical filaments, and antibodies to tau labeled tangles and plaque neurites in Alzheimer brain tissue. The results suggest tau is a major component of these filaments.
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The activity of the pyruvate dehydrogenase complex (PDHC) was reduced in affected areas of brain from patients with Huntington disease (caudate, putamen) and Alzheimer disease (frontal cortex) where choline acetyltransferase (CAT) activity was low.
Why it matters
This study found reduced activity of an energy-producing enzyme complex in affected brain areas of people with Huntington's and Alzheimer's disease. The authors state this deficiency may play a role in disease processes but does not appear to be a primary defect, and no treatment is tested.
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Scanning electron microscopy with energy-dispersive x-ray spectrometry was used to analyze the elemental content of neurofibrillary tangle (NFT)-bearing and NFT-free neurons within the Sommer's sector (H1 region) of the hippocampus in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia and in neurologically normal controls.
Why it matters
This preliminary study found aluminum accumulation in tangle-bearing neurons of Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia. It concerns those conditions and does not test any treatment, cure or prevention for Alzheimer's disease.
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In patients with Down syndrome, senile plaques and neurofibrillary tangles accumulate in the cortex at an earlier age than in persons of normal karyotype.
Why it matters
Among 20 people with Down syndrome dying after age 30, all had neocortical plaques and tangles but only 3 had been demented, and among 12 studied quantitatively at least 8 had plaque and tangle densities comparable to demented older people while only 1 had dementia. This shows that Alzheimer-like brain changes and dementia can be dissociated in Down syndrome, and it reports no treatment or cure.
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Choline acetyltransferase activity (presynaptic cholinergic system) and high affinity binding of cholinergic antagonists (postsynaptic cholinergic system) were measured in brain tissue removed after death from both mentally normal and demented old people.
Why it matters
In postmortem brain tissue, presynaptic cholinergic markers appeared selectively reduced in non-vascular senile dementia of the Alzheimer type, while markers were not significantly reduced in mixed senile and vascular dementia. The authors suggest centrally acting anticholinesterases might be beneficial, particularly early, but no treatment was tested.
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Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk.
Why it matters
In this large UK Biobank sample, people with both type 2 diabetes and depression had poorer cognitive performance and a higher 15-year dementia incidence, and several apoptosis-related proteins were linked to dementia risk. The study identifies proteins that may help predict dementia in this group, but it does not test any treatment or show that changing these proteins affects dementia risk.
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Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of α-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy.
Why it matters
The ActiTect machine learning pipeline identified REM sleep behavior disorder, a prodromal marker of α-synucleinopathies, from wrist-worn actigraphy recordings with strong discrimination across multiple cohorts. This is a screening tool for a risk marker and does not treat, cure, or prevent Alzheimer's disease.
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A total of 12 studies were included, with overall moderate risk of bias, mainly due to inadequate randomization and blinding.
Why it matters
Pooling 12 animal studies, this meta-analysis found that boosting TREM2, a receptor on microglia (the brain's immune cells), reduced amyloid plaque number and area in APP/PS1 mice, with stronger effects in younger mice; phosphorylated tau also fell. Overall risk of bias was moderate, mainly because of inadequate randomization and blinding. Because these are mouse results, they point to TREM2 as a possible treatment target whose benefit may depend on disease stage, not to a proven therapy for people.
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Tau accumulates in a group of neurodegenerative diseases known as tauopathies.
Why it matters
In human neurons, a disease-causing mutation in the MAPT gene was sufficient to disrupt multiple steps of the autophagy-lysosome pathway and cause Tau to accumulate in dysfunctional lysosomes. Pharmacological enhancement of autophagy improved cargo clearance and lowered Tau levels in this cell model, suggesting that boosting autophagy may help restore Tau homeostasis in tauopathies, but this is early laboratory work.
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= 0.025) over 3 years. NfL was not significantly associated with any MRI cSVD marker.
Why it matters
In middle-aged adults, plasma GFAP levels were associated with later changes in white matter integrity, while NfL was not significantly associated with any MRI marker of cerebral small vessel disease, and longitudinal changes in both biomarkers showed no significant associations with concurrent MRI progression. This suggests GFAP might help identify people at risk of small vessel disease years in advance, but it is a biomarker finding, not a treatment or cure.
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A significant ADI × dementia interaction was observed for global atrophy (p = .005) and several other outcomes.
Why it matters
This brain bank study found that people with dementia living in the most disadvantaged neighborhoods had greater brain shrinkage than those without dementia. It suggests socioeconomic disadvantage may worsen dementia-related brain changes, but it does not test any treatment or prevention.
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The empirical language composite showed superior and consistent sensitivity (faster decline rate) with all three biomarkers.
Why it matters
A combined language measure was more sensitive to decline alongside three plasma biomarkers than individual language tests. This may help monitor early progression, but it is a longitudinal observational finding and does not show a treatment effect.
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The final sample included 1196 cases (505 PD, 26 APD, 476 AD, 189 ALS) and 44,107 control subjects.
Why it matters
In this UK Biobank analysis, higher plasma NfL was linked to later diagnosis of several neurodegenerative diseases including Alzheimer's disease, while higher GFAP was linked specifically to Alzheimer's disease. These blood markers may help identify people at risk of these diseases for future neuroprotective treatments, though the study does not test any treatment itself.
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Five WMH clusters emerged. Compared to those with low WMH burden, participants in the mild occipital and high parieto-occipital clusters had faster memory decline; mild fronto-parietal and high parieto-occipital clusters showed faster executive decline; and mild and high fronto-parietal and high parieto-occipital clusters had faster language decline.
Why it matters
In this longitudinal study, five patterns of white matter hyperintensity distribution were identified, and several patterns were associated with faster decline in memory, executive function, or language. Posterior white matter hyperintensities were most associated with memory decline, and even mild white matter hyperintensities accelerated decline in some domains, but the study does not test any treatment, cure, or prevention.
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50/100
The AI-powered pipeline achieved robust performance with intraclass correlation coefficients exceeding 0.97 for regional uptake estimation compared with MR-based ground truth.
Why it matters
An AI pipeline quantified flortaucipir tau-PET uptake without needing structural MRI, with high agreement to MR-based measures, and elevated uptake in the entorhinal cortex and inferior temporal gyrus predicted future cognitive decline. This is a diagnostic and monitoring tool, not a treatment, cure, or prevention.
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Neuroinflammation drives Alzheimer's disease (AD) pathogenesis.
Why it matters
In mice, blocking the ZBP1-RIPK1 immune pathway reduced neuroinflammation, amyloid pathology and behavioral deficits. This is early animal work identifying a possible target, not a proven treatment for people.
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< 0.001). This study suggests 2 molecular pathways underlying CAA, with a larger effect size for the pathway including SFRP1 and APOE protein and C-terminally truncated Aβ before position 40.
Why it matters
This observational study suggests two molecular pathways involving proteins such as SFRP1 and APOE that are associated with cerebral amyloid angiopathy in older adults. Because it is cross-sectional, it cannot show cause and effect.
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The identification of biomarkers predicting the burden of brain alpha-synuclein (α-syn) pathology in vivo represents a research priority in Lewy body disease (LBD).
Why it matters
This study applied an endpoint dilution RT-QuIC assay to postmortem cerebrospinal fluid and found that seeding dose values differed significantly among Lewy body disease stages and correlated with pathology burden. It supports a biomarker for Lewy body pathology but does not offer a treatment or cure.
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Superficial white matter (SWM), containing short-range association connections beneath the cortex, has been affected in mild cognitive impairment and AD, with gaps in understanding the disease's early stages.
Why it matters
This study examined the microstructure of superficial white matter connections in the brain and found differences along early stages of the Alzheimer's disease continuum, including in cognitively intact people with positive pathology. It is an observational imaging study and does not test any treatment, cure, or prevention.
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Cross-sectional studies suggest a limited relationship between accelerated epigenetic aging derived from epigenetic clocks, and Alzheimer's disease (AD) pathophysiology or risk.
Why it matters
Two blood-based epigenetic clocks, DNAmPhenoAge and DNAmGrimAge, predicted progression from cognitively normal aging to mild cognitive impairment or Alzheimer's disease and were linked to cortical thinning and white matter disease burden. This is not a treatment or cure, but it suggests these blood measures may help predict risk and track disease-related brain changes.
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= 0.81). NfL levels were not significantly associated with GDS-15 in a population of community-dwelling older adults without dementia.
Why it matters
Plasma NfL was not significantly associated with depressive symptoms in community-dwelling older adults without dementia, with only exploratory signals in those with mild cognitive impairment. This is a cross-sectional finding and does not inform treatment, cure or prevention.
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.
- Precision prevention in exercise: Integrating OMICS biomarkers and artificial intelligence for injury risk assessment
- Gut microbiota and associated metabolites: key players in high-fat diet-induced chronic diseases
- Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10
- R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family: Clinical, Genetic, and Neuropathological Study
- Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice
- Chronic caffeine consumption prevents obesity-induced cognitive and memory impairments by reducing neuroinflammation and enhancing neuronal activity in the hippocampus
- Differential expression of interferon-gamma receptor on human glial cells in vivo and in vitro
- Structure of pathological TDP-43 filaments from ALS with FTLD
- Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development
- Reduction in neurons immunoreactive for calcium-binding proteins in the anteroventral thalamic nuclei of individuals with Down syndrome