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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Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer's disease (AD).
Why it matters
In lab experiments, this study identified lipoprotein particles (including LDL) and apolipoproteins, including APOE and CLU/APOJ, as molecules that the microglial protein TREM2 binds; disease-associated TREM2 mutations "abolished or reduced" that binding. Cells made to produce normal TREM2 took up more LDL, CLU and APOE than cells with the disease variants, microglia lacking Trem2 took up less LDL and CLU, and amyloid-beta bound to lipoproteins was taken up by microglia "in a TREM2-dependent fashion." This is cell-level work that describes a possible mechanism; it did not study patients or test any treatment.
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The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders.
Why it matters
In a large family with late-onset Alzheimer's disease, the R47H variant of TREM2, a microglial immune gene, cosegregated with 75% of cases. This is a genetic and neuropathological study of risk and reports no treatment, cure or prevention.
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This study suggests that information obtained from evaluating a subgroup of AD or MCI subject using second-generation TSPO tracers can be translated to the entire AD and MCI population.
Why it matters
This study found that people with different TSPO genotypes had the same level of amyloid load, and that TSPO genotype did not affect cognitive decline, suggesting results from one TSPO subgroup can apply to the whole Alzheimer's and mild cognitive impairment population. It is about how to interpret neuroinflammation imaging, not about treating, curing or preventing the disease.
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55/100
Traumatic brain injury (TBI) is an established risk factor for the early development of dementia, including Alzheimer's disease, and the post-traumatic brain frequently exhibits neurofibrillary tangles comprised of aggregates of the protein tau.
Why it matters
In mice, this study found that the brain's "glymphatic" fluid pathway helps clear tau, and that after a traumatic brain injury this pathway worked about 60% less well for at least a month. Mice lacking the water-channel protein aquaporin-4 had worse clearance after injury and developed more tau tangles and nerve-cell damage. The authors suggest this lasting drop in clearance "may be a key factor" in why injured brains become vulnerable to tau buildup, but this is animal research and tests no treatment for people.
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Mitochondrial DNA instability disorders are responsible for a large clinical spectrum, among which amyotrophic lateral sclerosis-like symptoms and frontotemporal dementia are extremely rare.
Why it matters
In one large family, a mutation in the CHCHD10 gene was linked to a late-onset condition including motor neuron disease and cognitive decline resembling frontotemporal dementia, with signs of mitochondrial problems. This is genetic research into a rare disorder and does not test any treatment, cure or prevention for Alzheimer's disease.
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Mitochondria and the endoplasmic reticulum (ER) form tight structural associations and these facilitate a number of cellular functions.
Why it matters
This study shows that the ER protein VAPB interacts with the mitochondrial protein PTPIP51 to regulate associations between the endoplasmic reticulum and mitochondria, and that these associations are disrupted by ALS/FTD-associated TDP-43. It concerns cellular mechanisms in ALS and FTD, not Alzheimer's disease, and reports no Alzheimer's treatment, cure or prevention.
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The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly.
Why it matters
This study found that extracellular miRNAs in cerebrospinal fluid and serum from Alzheimer's and Parkinson's patients correlate with disease status and features of pathology. 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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Most patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase β-amyloid burden as measured by amyloid imaging.
Why it matters
In this cross-sectional study of patients with subcortical vascular mild cognitive impairment and amnestic mild cognitive impairment, amyloid burden was associated with cognitive impairment in multiple domains in the vascular group but only with memory dysfunction in the amnestic group, and a significant interaction was found. The study describes how vascular disease and amyloid burden relate to cognition and does not test any treatment, cure or prevention.
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Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients.
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The RNA-binding protein TDP-43 regulates RNA metabolism at multiple levels, including transcription, RNA splicing, and mRNA stability.
Why it matters
In lab and live-animal experiments, this study found that TDP-43, a protein that clumps in ALS and some frontotemporal dementias, packs mRNA into granules that travel along neurons and help deliver it to distant parts of the cell. ALS-causing TDP-43 mutations impaired this transport, including in motor neurons grown from stem cells of ALS patients with any of three different mutations. The authors call this a "partial loss" of a newly described function. It is basic research on ALS, not Alzheimer's, and not a treatment study.
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The GGGGCC (G4C2) intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
In neuronal cell lines and zebrafish embryos, expanded G4C2 repeats formed RNA foci, bound RNA binding proteins including hnRNP-H, and caused apoptotic cell death. This points to RNA toxicity as a possible mechanism in C9ORF72-related ALS and FTD, but it is early laboratory work, not a treatment.
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Defects in DNA repair have been extensively linked to neurodegenerative diseases, but the exact mechanisms remain poorly understood.
Why it matters
The FUS protein was found to be important for the DNA damage response through interaction with HDAC1, and FUS proteins with familial ALS mutations were defective in DNA repair. This is laboratory and patient-cell research into disease mechanisms, not a treatment, cure or prevention.
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Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia.
Why it matters
In 1,587 stroke- and dementia-free participants, greater arterial stiffness was associated with lower total brain volume, more white matter hyperintensities, silent infarcts, and worse memory. This is an observational study and does not show that treating arterial stiffness prevents or cures Alzheimer's.
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Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain.
Why it matters
In six healthy volunteers, dehydration significantly reduced gray and white matter volume and expanded the ventricular system, changes similar to those reported in mild cognitive impairment and Alzheimer's disease. This means hydration status could be a confound in brain volume studies of these conditions.
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Micrographia was found in nearly half of the PD cohort.
Why it matters
In 68 men with Parkinson's disease, micrographia was identified in 63.2% and correlated significantly with disease severity, motor impairment, cognitive impairment, bradykinesia and hypophonia. This case-control study describes a clinical feature and does not test treating, curing or preventing Alzheimer's disease.
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Tar DNA Binding Protein-43 (TDP-43) is a principle component of inclusions in many cases of frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS).
Why it matters
In cultured cells, most inclusions of the protein TDP-43 — a main component of the protein clumps seen in ALS and frontotemporal lobar degeneration (FTLD-U) — overlapped with stress granules, and disease-linked TDP-43 mutations increased inclusion formation under stress; drugs that block protein translation suppressed inclusions from both normal and mutant TDP-43 in these cells. TDP-43 inclusions in post-mortem brain tissue also overlapped with stress-granule markers TIA-1 and eIF3, which the authors say supports TDP-43 taking part in the stress-granule pathway. This is laboratory work on ALS/FTLD rather than Alzheimer's, and no treatment was tested in animals or patients.
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We found reduced ¹²³I-FP-CIT binding in the striatum (p=0·045) in 17 (40%) of 43 participants compared with 18 controls, and substantia nigra hyperechogenicity in 14 (36%) of 39 participants with IRBD, compared with 16 (11%) of 149 controls (p=0·0002).
Why it matters
In this prospective study, some patients with idiopathic rapid-eye-movement sleep behaviour disorder showed reduced striatal dopamine transporter binding or substantia nigra hyperechogenicity compared with controls. These neuroimaging findings might be useful markers to identify individuals at increased risk for development of synucleinopathies.
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The in vivo measure of cerebral amyloidosis known as [(11)C]PiB is associated with cross-sectional regionally specific brain atrophy and longitudinal cognitive decline in multiple cognitive domains that occur before the clinical diagnosis of Alzheimer disease.
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The role of microglial cells in the pathogenesis of Alzheimer's disease (AD) neurodegeneration is unknown.
Why it matters
This study examined human brain tissue and reports that dystrophic (senescent) microglia, rather than activated ones, are found at sites of tau pathology. It notes that anti-inflammatory drugs do not prevent or reverse tau pathology, so it offers no treatment or cure.
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Inclusions of TAR DNA-binding protein-43 (TDP-43), a nuclear protein that regulates transcription and RNA splicing, are the defining histopathological feature of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-Us) and sporadic and familial forms of amyotrophic lateral sclerosis (ALS).
Why it matters
In cells, a roughly 25-kDa piece of the protein TDP-43, the fragment left when the enzyme caspase cuts it, formed toxic, insoluble clumps. The study suggests it kills cells by a new toxic effect ("gain of function") rather than by disabling normal TDP-43, and phosphorylation was not needed for that. The authors also report that this fragment is found specifically in the abnormal protein clumps of human TDP-43 diseases such as FTLD-U and ALS. This is laboratory work on ALS and frontotemporal lobar degeneration, not Alzheimer's, and it does not test any treatment.
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The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry.
Why it matters
This review proposes a revised dopamine hypothesis of schizophrenia that links risk factors to increased presynaptic striatal dopaminergic function. It is about schizophrenia, not Alzheimer's disease, and offers no treatment, cure or prevention for Alzheimer's disease.
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Neurotoxic amyloid beta peptide (Abeta) accumulates in the brains of individuals with Alzheimer disease (AD).
Why it matters
In mice, apoE slowed the removal of amyloid beta from the brain across the blood-brain barrier, and the apoE4 form did so more than apoE2 or apoE3. The authors report that amyloid beta bound to apoE4 was moved from a fast exit route (the LRP1 receptor) to a slower one (the VLDL receptor). They say this "might contribute" to how APOE genotype affects Alzheimer's, but this was tested only in animals and does not show a treatment for people.
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Tau form ratio was significantly reduced in patients with PSP (0.504 +/- 0.284) when compared to age-matched controls (0.989 +/- 0.343), and to patients with other neurodegenerative conditions (range = 0.899-1.215).
Why it matters
A ratio of two tau forms in cerebrospinal fluid was significantly reduced in people with progressive supranuclear palsy compared with controls and people with other neurodegenerative conditions, including Alzheimer disease. This concerns a biomarker for diagnosing progressive supranuclear palsy, not a treatment, cure or prevention for Alzheimer's disease.
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An a priori defined cutoff value of p-tau(231) yields relatively stable results across centers, suggesting a good feasibility of a standard criterion of p-tau(231) for the prediction of Alzheimer disease.
Why it matters
In a multicenter study of people with mild cognitive impairment, levels of a specific form of tau in spinal fluid predicted who would go on to develop Alzheimer's disease, independent of age, gender, mental test scores and APOE genotype. An a priori cutoff value worked fairly consistently across centers, suggesting it could be a feasible standard criterion for predicting Alzheimer's disease.
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The endosomal sorting complexes required for transport (ESCRTs) are required to sort integral membrane proteins into intralumenal vesicles of the multivesicular body (MVB).
Why it matters
In cells, blocking ESCRT subunits or expressing CHMP2B mutants stopped autophagy and caused protein aggregates to build up, and working multivesicular bodies were needed to clear TDP-43 and polyglutamine aggregates. These are cell-based findings that suggest a mechanism but do not show a therapy for 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.
- Down syndrome with partial duplication and del (21) syndrome: study protocol and call for collaboration. Study I: Clinical assessment
- Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study
- Effects of Exercise on Urinary AD7c-NTP (Alzheimer-Associated Neuronal Thread Protein) Levels and Cognitive Function Among Active Korean Elderly: A Randomized Controlled Trial
- Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death
- Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated
- Synaptic proteins, neuropathology and cognitive status in the oldest-old
- Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling
- Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
- Elimination of amyloid precursor protein in senile plaques in the brain of a patient with Alzheimer-type dementia and Down syndrome
- Reduced telomere length in older men with premutation alleles of the fragile X mental retardation 1 gene