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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Polymorphisms of the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been reported to be potentially associated with the risks of developing frontotemporal lobar degeneration (FTLD), with inconsistent conclusions.
Why it matters
Pooling eight studies, this meta-analysis found that two TREM2 gene variants, rs75932628 and rs2234253, were associated with a higher risk of frontotemporal lobar degeneration in Caucasian populations, while two other variants showed no difference. The findings concern frontotemporal lobar degeneration rather than Alzheimer's.
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Dominance of 4R over three-repeat (exon 10-) tau isoforms contrasts with earlier reports of R406W patients and was not sufficiently explained by the presence of H1/H2 haplotypes in two of the autopsied patients.
Why it matters
This report followed seven members of a new Swedish family carrying the MAPT R406W mutation for up to 22 years and reviewed 63 previously described carriers plus 3 with two copies. Across all cases, the median age of onset was 56 years and the illness lasted a median of 13 years, with memory loss most common and Alzheimer's disease the most frequent clinical diagnosis even though amyloid-β pathology was absent in the autopsied family members. It suggests this tau-driven inherited disease can look much like Alzheimer's in the clinic.
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Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined.
Why it matters
This post-mortem study found that brain pathology in behavioural-variant frontotemporal dementia is distributed asymmetrically between the two hemispheres, not always worse on the right. It is a descriptive pathology study and does not test any treatment, cure or prevention.
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In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by β-secretase to generate a 99-aa C-terminal fragment (C99) that is then cleaved by γ-secretase to generate the β-amyloid (Aβ) found in senile plaques.
Why it matters
In cell models, increased unprocessed C99 in mitochondria-associated membranes altered lipid composition and mitochondrial function, which the authors suggest may contribute to the energy defects seen in Alzheimer's. This is laboratory cell work, not a study in people, and does not test any treatment or show that targeting this process helps patients.
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Patients with CBS without typical AD pathology exhibited AV-1451 retention in the motor cortex, corticospinal tract, and basal ganglia contralateral to the affected body side, clearly different from controls and patients with AD dementia or PSP.
Why it matters
In 8 patients with corticobasal syndrome, the tau PET tracer 18F-AV-1451 showed retention in the motor cortex, corticospinal tract and basal ganglia on the side opposite the most affected body side, unlike the pattern seen in Alzheimer's disease dementia. This small imaging study is about distinguishing conditions, not about treating, curing or preventing Alzheimer's disease.
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Conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of late onset sporadic Alzheimer's disease (LOAD).
Why it matters
In a mouse model of early Alzheimer's pathology, deficiency of TYROBP was neuroprotective. This is animal work on a possible mechanism and does not establish a treatment, cure, or prevention in people.
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Down syndrome (also known as trisomy 21) is the model human phenotype for all genomic gain dosage imbalances, including microduplications.
Why it matters
This review discusses how having an extra copy of chromosome 21 leads to the features of Down syndrome, including Alzheimer's disease, and how studying this could reveal ways to modify the risk of these features. It describes a research approach and does not report a treatment or cure.
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Genetic variations in the myeloid immune receptor TREM2 are linked to several neurodegenerative diseases.
Why it matters
In lab studies of TREM2 protein and cells, mutations found in Nasu-Hakola disease were buried inside the protein and reduced its stability, so less folded TREM2 reached the cell surface. Alzheimer's disease risk variants sat on the protein's surface and affected its binding to a TREM2 ligand, which the authors describe as two distinct loss-of-function mechanisms. This is laboratory work on proteins and cells, not a study of patients, risk or treatment.
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Hypertension is a leading risk factor for dementia, but the mechanisms underlying its damaging effects on the brain are poorly understood.
Why it matters
In mouse models of hypertension, perivascular macrophages drove blood vessel and cognitive problems through a pathway involving angiotensin II, angiotensin type 1 receptors and the enzyme NOX2. The authors propose these cells as a possible therapeutic target, but this is animal research and no treatment is proven.
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Defective autophagy contributes to Alzheimer disease (AD) pathogenesis although evidence is conflicting on whether multiple stages are impaired.
Why it matters
This study examined autophagy-related genes in CA1 pyramidal neurons from early and late-stage Alzheimer's disease subjects and nondemented controls, finding increased induction that appeared to overburden failing lysosomes. It describes a cellular process in brain tissue and does not report a treatment, cure, or prevention.
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51/100
Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system to adjust behavior to environmental stimuli and to control body functions, memories, and emotions.
Why it matters
This review discusses how problems with synapses, the connections between nerve cells, contribute to several brain disorders including Alzheimer's disease. It suggests that targeting synapse dysfunction could be a future treatment approach, but no specific treatment is tested or proven here.
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A soluble fragment (sTREM2) is often found abnormally increased in cerebrospinal fluid (CSF) in Alzheimer's disease (AD).
Why it matters
In 114 participants, higher levels of the soluble TREM2 protein in spinal fluid were linked to greater gray matter volume and reduced water diffusivity in people with mild cognitive impairment. This is an observational association and does not show that measuring or changing sTREM2 treats or prevents Alzheimer's disease.
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Improved short-term survival after stroke has necessitated quantifying risk and risk factors of long-term sequelae after stroke (ie, recurrent stroke and dementia).
Why it matters
This study estimated the long-term risk of recurrent stroke and poststroke dementia and how much of that risk is attributable to cardiovascular risk factors before the first stroke. It is an observational study, so it cannot prove that controlling these risk factors prevents poststroke dementia.
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51/100
A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD).
Why it matters
In cell lines, primary neurons, and patient-derived iNeurons, reduced C9orf72 expression attenuated autophagy and caused accumulation of p62-positive puncta, and basal autophagy was markedly reduced in C9ALS/FTD patient-derived iNeurons. The findings suggest C9orf72 haploinsufficiency and reduced autophagy might underlie C9ALS/FTD-associated p62 pathology, but no treatment or cure is reported.
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Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis.
Why it matters
This review describes how frontotemporal dementia cases can be grouped by which protein accumulates in the brain, including tau, TDP-43, or FET proteins. It concerns frontotemporal dementia, not Alzheimer's disease, and does not report any treatment, cure, or prevention for Alzheimer's.
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Neurodegenerative diseases (NDDs) are characterized by selective dysfunction and loss of neurons associated with pathologically altered proteins that deposit in the human brain but also in peripheral organs.
Why it matters
This review discusses molecular pathological classification of neurodegenerative diseases based on morphological evaluation of protein deposits and their distribution. It notes that proteins and their modifications can potentially be targeted for therapy or used as biomarkers, but it does not test any treatment, cure, or prevention.
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Neuroinflammation and synaptic degeneration are major neuropathological hallmarks in Alzheimer's disease (AD).
Why it matters
This study analyzed cerebrospinal fluid from 95 individuals and found that neurogranin and YKL-40 are elevated in people with dementia or mild cognitive impairment due to Alzheimer's disease. These are markers of synaptic damage and inflammation, not a treatment, cure, or prevention.
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Alzheimer's disease (AD) is characterized by synaptic failure, dendritic and axonal atrophy, neuronal death and progressive loss of cognitive functions.
Why it matters
Using viral gene transfer to raise APPsα in an Alzheimer's mouse model rescued synaptic failure, suggesting loss of normal APP function may contribute to the disease. This is animal gene therapy research and not a proven treatment for people.
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Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of frontotemporal dementia and motor neuron disease.
Why it matters
In 35 C9ORF72 mutation cases, this study counted different dipeptide repeat protein inclusions in the brain and found their amounts varied, with no evidence of soluble forms. It is a pathology study of a genetic cause of frontotemporal dementia and motor neuron disease and does not test any treatment or cure.
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Currently no effective disease-modifying agents exist for the treatment of Alzheimer disease (AD).
Why it matters
The Src family kinase inhibitor AZD0530 was tested in Alzheimer mice to see whether Fyn inhibition could prevent or delay disease progression. This is animal work repurposing a cancer drug, so it is not yet established as a treatment for people.
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Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia.
Why it matters
This review proposes insulin resistance as the key link between metabolic syndrome and Alzheimer's disease, noting that Alzheimer's patients show impaired insulin signaling similar to that in metabolic syndrome. It states that several diabetes therapies that enhance insulin signaling are being tested for potential benefit in Alzheimer's disease and dementia, so no treatment is established.
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Alzheimer disease (AD) is associated with an increase in the brain of the 18-kDa translocator protein (TSPO), which is overexpressed in activated microglia and reactive astrocytes.
Why it matters
This study tested whether a simpler PET imaging method using the cerebellum as a reference region could replace the standard method that requires arterial blood sampling to measure TSPO, a marker of activated microglia and astrocytes in Alzheimer's disease. The findings suggest this simpler approach may work for detecting neuroinflammation, but the study involved only 21 healthy controls, 11 people with mild cognitive impairment, and 25 Alzheimer's patients.
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Triggering receptor expressed on myeloid cells 2 (TREM2) gene is a recently identified susceptibility gene for Alzheimer's disease (AD), as its low-frequency variants increase the risk of this disease with an odds ratio similar to that of an APOE ɛ4 allele.
Why it matters
In APPswe/PS1dE9 mice, a transgenic model of Alzheimer's disease, the authors report that TREM2 rose in microglia, the brain's immune cells, as the disease advanced, and they attribute that rise to higher amyloid-β(1-42). In cultured microglia, TREM2 "facilitated Aβ(1-42) phagocytosis and inhibited Aβ(1-42)-triggered proinflammatory responses," and the study's title reports that raising TREM2 in the mice reduced neuropathology and improved spatial memory. This is mouse and cell work with no human data, and this record gives no sizes or methods for the memory result.
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TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia.
Why it matters
TREM2 mutations were first linked to Nasu-Hakola disease, a rare inherited condition with bone cysts and early dementia. This case report describes two siblings in one consanguineous Italian family who had early-onset, recessively inherited frontotemporal lobar degeneration with a TREM2 p.Thr66Met variant, but without severe bone disease. Their illness had unusual features, including parkinsonism, epilepsy and early parietal and hippocampal involvement. As a single-family report it cannot show how common this variant is or what risk it carries, and it does not study Alzheimer's disease.
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TAR DNA-binding protein (TDP-43, also known as TARDBP) is the major pathological protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
This laboratory study reports differing roles of the ubiquitin proteasome system and autophagy in clearing TDP-43, the major pathological protein in ALS and frontotemporal dementia. It is cell-based work on disease mechanisms and does not test a treatment in patients.
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.
- Serotonin (5-HT) in brains of adult patients with Down syndrome
- Prion Diseases
- Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
- Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions
- Pathological tau disrupts ongoing network activity
- The concentration-dependent protective effects by new generation hypoglycemic agents on delirium, depression, dementia and coma: evidence from a network meta-analysis
- Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
- Cortical microinfarcts on 3T MRI: Clinical correlates in memory-clinic patients
- Increased plasma levels of lipocalin 2 in mild cognitive impairment
- The bidirectional lung brain-axis of amyloid-β pathology: ozone dysregulates the peri-plaque microenvironment