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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Why it matters
An update on the naming and classification of the neuropathologic subtypes of frontotemporal lobar degeneration.
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The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.
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Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder characterized by aggregates of the microtubule-associated protein tau (MAPT).
Why it matters
This case-control study looked at whether dementia and parkinsonism run in families of people with progressive supranuclear palsy (PSP), a disorder related to tau protein. It is about understanding family patterns of this rare disease and does not test any treatment, cure, or prevention for Alzheimer's.
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The two current major staging systems in use for Lewy body disorders fail to classify up to 50% of subjects.
Why it matters
Earlier staging systems for Lewy body disorders could not place up to half of cases, especially those with alpha-synuclein pathology only in the smell (olfactory) bulb or in limbic regions. Examining ten brain regions from 417 people after death, including people with Parkinson's disease, dementia with Lewy bodies and Alzheimer's disease with Lewy bodies, the authors proposed five stages that classified every case in this study. Higher stages went with generally worse dopamine-pathway damage, cognitive (MMSE) scores and movement (UPDRS Part 3) scores. This is an association across autopsied brains, not a measure of change in any one person.
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Why it matters
Reports that the classical complement cascade mediates synapse elimination in the central nervous system.
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Consistent with preclinical literature supporting the neuroprotective effects of lithium, long-term treatment is associated with preservation of recollective memory function and increased hippocampal size in vivo.
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To address computational and analytic challenges in whole-genome association studies (WGAS), researchers developed PLINK, an open-source C/C++ tool set.
Why it matters
Describes PLINK, a tool set for whole-genome association and population-based linkage analyses.
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Here, we investigated if TAR-DNA-binding protein-43 (TDP-43), the disease protein in frontotemporal lobar degeneration and ubiquitin inclusions with or without motor neuron disease as well as amyotrophic lateral sclerosis, also formed inclusions in Lewy body (LB) disorders including Parkinson's disease (PD) without or with dementia (PDD), and dementia with LBs (DLB) alone or in association with Alzheimer's disease (AD).
Why it matters
Examining 213 brains after death, the researchers looked for clumps of TDP-43, a protein best known from some frontotemporal dementias and ALS, and found them in 25 of 80 brains with both dementia with Lewy bodies and Alzheimer's, 4 of 21 with Parkinson's dementia and 5 of 69 with Parkinson's without dementia, but in none of 10 with Lewy body dementia alone and 1 of 33 healthy brains. The clumps were significantly more common in diseased than normal brains and in brains of people who had dementia, which the authors say suggests TDP-43 "may have co-morbid effects" in Lewy body diseases. This shows the proteins occurring together, not that TDP-43 causes the dementia, and the highest rate was in brains that also had Alzheimer's.
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Elevations in plasma Abeta(42) peptide levels are associated with earlier onset of AD and increased risk of death.
Why it matters
In 204 adults with Down syndrome followed over time, those who were not demented at the start and had middle or highest levels of plasma Abeta(42) were more than twice as likely to develop Alzheimer's disease as those with the lowest levels. Among all participants, those in the highest tertile of plasma Abeta(42) at baseline were more than twice as likely to die during the study period.
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TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND).
Why it matters
Across 193 cases, this study found that TDP-43 is a common pathological protein in most sporadic and familial frontotemporal lobar degeneration with ubiquitin inclusions, with or without motor neuron disease. It is a pathology study and does not test any treatment, cure or prevention.
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Molecular genetic studies of familial cases of FTLD-U have shown that mutations in the progranulin (PGRN) gene are a major genetic cause of FTLD-U. Thus, familial TDP-43 proteinopathy is associated with defects in multiple genes, and molecular genetics is required in these cases to correctly identify the causative gene defect.
Why it matters
This 2007 consensus statement sets out how frontotemporal lobar degeneration (FTLD), a group of dementias different from Alzheimer's disease, should be diagnosed and classified from brain tissue. Its summary reports that mutations in the progranulin (PGRN) gene are "a major genetic cause" of inherited FTLD-U, and that because inherited cases can involve "multiple genes," genetic testing "is required in these cases to correctly identify the causative gene defect." It is an expert consensus rather than a new study, and it is not about diagnosing, treating or preventing Alzheimer's disease.
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Microglia are the principal immune cells of the brain.
Why it matters
The study's title reports that, in a model of "Alzheimer-like disease", lacking Ccr2, a receptor the record says "mediates the accumulation of mononuclear phagocytes at sites of inflammation", impaired the build-up of microglia and accelerated disease progression. The authors frame this against an open question: microglia "may be neuroprotective by phagocytosing amyloid-beta (Abeta)", but their activation "may also cause neurodegeneration". The record we hold has only background text, with no methods, measures or numbers, and it tests no treatment in people.
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Additional studies seem to be warranted.
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59/100
Assessment of the cingulum fibers using diffusion tensor imaging may aid early diagnosis of Alzheimer disease.
Why it matters
Fractional anisotropy of the cingulum fibers was significantly reduced in mild cognitive impairment and even more in Alzheimer disease, and adding this measure to hippocampal volume improved separation of MCI and Alzheimer disease from normal aging. Assessment of cingulum fibers using diffusion tensor imaging may aid early diagnosis.
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59/100
Null mutations in the progranulin gene (PGRN) were recently reported to cause tau-negative frontotemporal dementia linked to chromosome 17.
Why it matters
In 378 people with frontotemporal lobar degeneration (FTLD), mutations in the progranulin gene were found in 10%, and in 23% of those with a family history. However, the rate "dropped to 5%" in a less selected group of 167 patients from Alzheimer's research centres, where progranulin mutations were "equally frequent as mutations in the tau gene (MAPT)". All 23 mutations described lead to loss of working progranulin. Carriers often first showed language problems, and their age at onset varied widely. This is a genetic study of FTLD, not Alzheimer's disease, and it tests no treatment.
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Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects.
Why it matters
This study examined whether higher dietary intake of folate, vitamin B12 and vitamin B6 is linked to lower risk of Parkinson disease, not Alzheimer's disease. It is a cohort study of people aged 55 and older in the Rotterdam Study, so it does not provide evidence about treating, curing or preventing Alzheimer's.
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Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge.
Why it matters
Describes Gene Set Enrichment Analysis (GSEA), a method and free software package for interpreting gene expression data by looking at groups of genes that share a biological function, chromosomal location or regulation. Its examples come from cancer data sets; it is not about Alzheimer's.
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Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits.
Why it matters
Mice making a human tau variant that could be switched off developed tangles, nerve cell loss and behavioural problems. After the tau was switched off, memory recovered and nerve cell numbers stabilised even though tangles kept building up, so tangles were not sufficient to cause memory decline or nerve cell death in this model.
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Familial parkinsonism and dementia with cortical and subcortical Lewy bodies is uncommon, and no genetic defect has been reported in the previously described sibships.
Why it matters
In one Spanish family with autosomal dominant parkinsonism, dementia and visual hallucinations, this study found a novel E46K mutation in the alpha-synuclein gene and Lewy bodies in cortical and subcortical areas. It links this mutation to dementia with Lewy bodies, not to treating, curing or preventing Alzheimer's disease.
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We used MRI volume sampling with coregistered and atrophy corrected FDG-PET scans to test three hypotheses: 1) hippocampal formation measures are superior to temporal neocortical measures in the discrimination of normal (NL) and mild cognitive impairment (MCI); 2) neocortical measures are most useful in the separation of Alzheimer disease (AD) from NL or MCI; 3) measures of PET glucose metabolism (MRglu) have greater diagnostic sensitivity than MRI volume.
Why it matters
This 2001 study scanned healthy people, people with mild cognitive impairment (MCI) and people with Alzheimer's at a single point in time, using both MRI (brain tissue size) and FDG-PET (how much sugar brain cells use). In MCI, the authors found changes in the hippocampal memory region "without significant neocortical changes", while changes in the outer brain layer "best characterize AD"; in "most between group comparisons" the sugar-use measures separated the groups better than the size measures. These are group comparisons from one moment in time, and the record gives no group sizes or accuracy figures, so they do not show how well a scan would work for one person or what happens over time.
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Aggregated alpha-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders.
Why it matters
Nitrated alpha-synuclein was found in the characteristic inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy. This links oxidative and nitrative damage to these disorders but is a tissue-based finding with no treatment tested.
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Why it matters
Reports that two transmembrane aspartates in presenilin-1 are required for presenilin endoproteolysis and gamma-secretase activity.
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Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).
Why it matters
In brain tissue from people with inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), different tau gene mutations changed tau's forms in different, mutation-specific ways. In lab tests on engineered tau protein, all but one of the mutations studied weakened tau's ability to bind and build microtubules, the cell's internal support tracks, which implicates this loss of function in the disease. This is laboratory and post-mortem work on a rare inherited condition. It does not test a treatment and does not directly describe typical Alzheimer's disease.
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Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent.
Why it matters
Researchers found a mutation in the alpha-synuclein gene in an Italian family and in three unrelated families of Greek origin with inherited Parkinson's disease. The authors say this finding will help in understanding how the disorder develops.
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59/100
Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans.
Why it matters
This 1995 Nature paper describes transgenic mice that overexpress a mutant (V717F) form of the amyloid precursor protein, which its title says show "Alzheimer-type neuropathology". It was motivated by APP mutations "tightly linked to autosomal dominant forms of AD" and by "the lack of an animal model"; our record does not say which brain changes the mice developed, at what age, or whether memory was affected. These are mice, not people, so the study does not show how to treat or prevent Alzheimer's in humans.
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.
- Evaluating the effects of liraglutide, empagliflozin and linagliptin on mild cognitive impairment remission in patients with type 2 diabetes (LIGHT-MCI): study protocol for a multicentre, randomised controlled trial with an extension phase
- Chronic traumatic encephalopathy: a potential late effect of sport-related concussive and subconcussive head trauma
- Targeted delivery of nerve growth factor via encapsulated cell biodelivery in Alzheimer disease: a technology platform for restorative neurosurgery
- Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein
- Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer's disease
- DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay
- Fornix and hippocampal atrophy in traumatic brain injury
- Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity?
- The amyloid precursor protein: a biochemical enigma in brain development, function and disease
- Amino-terminally truncated Abeta peptide species are the main component of cotton wool plaques