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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Depending on the species, microglial cells represent 5-20% of glial cells in the adult brain.
Why it matters
This review describes the many roles of microglia in the brain and their contribution to conditions including Nasu-Hakola disease and age-related neurodegenerative diseases such as Alzheimer's. It is a summary of biology and does not report a treatment, cure or prevention.
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49/100
Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively.
Why it matters
In cells from patients with C9orf72 frontotemporal dementia/ALS and in flies, small molecules that stabilize a specific RNA structure reduced two key pathologies and improved survival. These are early laboratory and animal findings for a different condition and have not been shown to treat or prevent Alzheimer's disease in people.
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49/100
More than 40 diseases, most of which primarily affect the nervous system, are caused by expansions of simple sequence repeats dispersed throughout the human genome.
Why it matters
This review covers more than 40 diseases caused by expansions of simple sequence repeats, including C9ORF72 in ALS/frontotemporal dementia and Huntington disease, and discusses their varied molecular mechanisms. It provides clinical and genetic descriptions but reports no treatment, cure, or prevention for Alzheimer's disease.
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Triggering receptor expressed in myeloid cells (TREM2) is a member of the immunoglobulin superfamily and is expressed in macrophages, dendritic cells, microglia, and osteoclasts.
Why it matters
This laboratory work identified ADAM17 as the main protease that releases the TREM2 ectodomain and showed it cleaves TREM2 after Histidine 157. It describes basic TREM2 biology only and provides no evidence about treating, curing or preventing Alzheimer's disease.
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Alzheimer's disease (AD) not only involves loss of memory functions, but also prominent deterioration of sleep physiology, which is already evident at the stage of mild cognitive impairment (MCI).
Why it matters
In 16 patients with mild cognitive impairment, a type of brain stimulation during a daytime nap improved sleep brain wave patterns and visual memory compared with sham stimulation. This is a small, early study of a possible therapy for sleep and memory problems in MCI, not a proven treatment or cure.
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Alzheimer's disease (AD) is the most common form of dementia and the 6th leading cause of death in the US.
Why it matters
This 2017 review summarises research showing that some versions of the TREM2 gene, which works in the brain's immune cells (microglia), 'greatly increase the risk' of Alzheimer's — which the authors take as a sign the immune system plays a central part in the disease. It covers lab findings on how microglia respond to amyloid plaques, but reports no new data and gives no size for the risk. The authors say this opens 'new avenues' for treatment research; the review itself reports no treatment, cure or prevention.
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Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease.
Why it matters
In a mouse model of multiple microinfarcts, this study investigated whether glymphatic pathway function, which helps clear interstitial solutes including amyloid beta and tau, is impaired. It is animal work and does not establish any treatment or prevention for Alzheimer's disease.
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Heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been reported to significantly increase the risk of developing Alzheimer's disease (AD).
Why it matters
In a strong amyloid mouse model (PS2APP), brain levels of soluble TREM2, a protein made by the brain's immune cells (microglia), "strongly increased with age," rising 211% between 5 and 16 months. The rise was compared against PET scans of microglial activation and amyloid plaque in the same animals. The authors suggest combining these scans with sTREM2 in future anti-inflammatory treatment trials. This is a one-time snapshot in mice that shows association only, and it reports no treatment, cure or prevention for people.
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Alzheimer's disease (AD) and frontotemporal dementia (FTD) are leading causes of cognitive decline.
Why it matters
This cross-sectional study used optical coherence tomography to compare retinal layer thickness in people with mild cognitive impairment, Alzheimer's disease, frontotemporal dementia and healthy controls. It examines a possible measurement of retinal changes, not a treatment or cure.
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Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets.
Why it matters
This is a meeting report summarizing expert discussion on neuroinflammation and innate immunity in conditions including Alzheimer disease. It does not report new treatment results, so it cannot yet say whether targeting innate immunity will help patients.
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The multiple roles played by RNA binding proteins in neurodegeneration have become apparent following the discovery of TAR DNA binding protein 43 kDa (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) involvement in amyotrophic lateral sclerosis and frontotemporal lobar dementia.
Why it matters
This review describes the normal functions and disease roles of TDP-43 and FUS/TLS proteins in ALS and frontotemporal dementia, and suggests that studying them may help develop therapies. It does not test any treatment or prevention for Alzheimer's disease, so it has no direct implications for treating, curing, or preventing the disease.
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Two recent studies have identified that a rare coding variant (p.R47H) in exon 2 of triggering receptor expressed on myeloid cells 2 (TREM2) gene is associated with Alzheimer's disease (AD) susceptibility in Caucasians.
Why it matters
In a Han Chinese cohort, the rare TREM2 R47H variant was rare or absent, and other newly identified variants in the gene were not significantly associated with Alzheimer's disease. This suggests TREM2's role as a risk gene may differ across populations, but it does not point to any treatment or prevention approach.
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In 1975, tau protein was isolated as a microtubule-associated factor from the porcine brain.
Why it matters
This review notes that almost 80 disease-causing tau gene mutations have been found in familial frontotemporal dementia but none in Alzheimer's disease, and that the first phase I clinical trial of an active tau immunization vaccine in Alzheimer's patients was recently completed. Assays for tau in cerebrospinal fluid and plasma are available, and tau radiotracers for PET are under development.
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Traumatic brain injury (TBI) is a risk factor for dementia.
Why it matters
In brains from 70 people who died after a single moderate or severe head injury, 40% of those who died within days and 47% of those who lived a year or more (up to 47 years) showed blood proteins leaking into brain tissue, a sign that the blood-brain barrier was damaged; 21 uninjured controls showed only limited staining. The authors call these data "preliminary": the study suggests barrier damage may start early and last for years after injury, but it did not measure dementia, did not study mild injuries or living patients, and tested no treatment.
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49/100
Aging is the principal demographic risk factor for Alzheimer disease (AD), the most common neurodegenerative disorder.
Why it matters
This study found that increasing klotho expression reduced premature mortality and network dysfunction and prevented depletion of certain cells in hAPP transgenic mice. It is animal research and does not establish that raising klotho treats or prevents Alzheimer's disease in people.
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We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene).
Why it matters
This study built a database of genome-wide gene activity across the lifespan in mice engineered to develop either amyloid plaques (mutant human APP and/or PSEN1) or tau tangles (mutant human MAPT), and checked it with qPCR and against human studies, including GWAS hits. Immune genes rose and fell in step with plaques, synaptic genes moved opposite to tangles, and the immune-gene network analysis gave Trem2 hub status only in the amyloid mice. These are correlations in mice; the study tests no treatment and makes no claim about preventing or reversing Alzheimer's in people.
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Functional and structural connectivity measures, as assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease (AD) and other disorders.
Why it matters
This 2014 review gathers MRI studies of how brain regions connect, functionally and structurally, across Alzheimer's, frontotemporal dementia and movement-related neurodegenerative diseases. It reports that these measures track symptom location and severity in Alzheimer's and frontotemporal dementia, and that cognitively healthy people with brain amyloid or genetic risk for Alzheimer's show functional connectivity changes "reminiscent of" those in symptomatic disease. The authors present connectivity as a "potential" early marker, not a proven test, and note that in movement-related diseases only structural connectivity, not functional, had consistently matched symptoms.
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49/100
This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily Alzheimer's disease (AD).
Why it matters
This review summarizes changes in microglia during aging and in Alzheimer's disease and compares humans with rodents. It reports no treatment that cures or prevents Alzheimer's disease.
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The long-term consequences of repetitive head impacts have been described since the early 20th century.
Why it matters
Drawing on 202 published cases, this review found that chronic traumatic encephalopathy, which follows repetitive head impacts, shows up as changes in mood (such as depression), behaviour (such as explosivity), and thinking and memory, and less often in movement. It proposes research criteria for "traumatic encephalopathy syndrome" with four subtypes. The authors stress these "are not meant to be used for a clinical diagnosis" and expect them to change. It tests no treatment and offers no way to prevent Alzheimer's disease.
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Aβ and vascular risk interact to enhance cortical thinning in posterior brain regions that are particularly vulnerable to AD.
Why it matters
In 66 older people with varying vascular risk, high vascular risk and amyloid deposits appeared to interact to produce thinner cortex in brain regions vulnerable to Alzheimer's disease. This is an observational study and does not prove that controlling vascular risk prevents dementia, though it supports further investigation.
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The neurodegenerative diseases are a diverse group of disorders characterized by progressive loss of specific groups of neurons.
Why it matters
This review summarizes evidence that FUS gene variants are causes or risk factors for ALS, essential tremor and rare forms of FTLD, and that FUS protein aggregates in several neurodegenerative diseases. It discusses possible future treatment and prevention but tests none.
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Type 2 diabetic patients develop aberrant functional connectivity of the PCC, which is associated with insulin resistance in selected brain regions.
Why it matters
In 30 people with type 2 diabetes, functional connectivity between the posterior cingulate cortex and other brain regions was altered, and one measure correlated with insulin resistance. This links insulin resistance to brain connectivity changes that may relate to Alzheimer's, but it is a small study and does not show that treating insulin resistance prevents dementia.
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The APOE ε4 allele segregated dose-dependently and selectively with CA1-SRLM thinning and worse episodic memory performance in a pool of older subjects across a cognitive spectrum.
Why it matters
In this small cross-sectional imaging study, carriers of the APOE ε4 allele had greater thinning of one hippocampal region and worse episodic memory. It shows an association between a gene, brain structure and memory but does not test any treatment.
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Dementia with Lewy bodies (DLB) is pathologically characterized by α-synuclein aggregates in the brain.
Why it matters
In 22 patients with dementia with Lewy bodies, total β-amyloid pathology scores correlated positively with total α-synuclein pathology scores, and the factors that correlated best with α-synuclein pathology were the severity of β-amyloid pathology and presence of the MAPT H1 haplotype. This is a small pathology study that describes how these protein deposits overlap and does not show a treatment, cure, or prevention.
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The APOE-ε4 allele correlates with increased risk of Alzheimer disease (AD) and increased parenchymal amyloid plaques.
Why it matters
In 371 autopsied brains, amyloid in blood-vessel walls (cerebral amyloid angiopathy) was worst in people with two copies of APOE-ε4: in the occipital lobe, 95% of these 22 brains had the highest meningeal score, against 19% of APOE-ε3/3 brains. Unexpectedly, APOE-ε2/3 brains, a genotype linked to lower Alzheimer's risk, had more of this vessel amyloid than ε3/3 (44% vs 19% in the occipital meninges). The authors conclude that APOE's link to vessel amyloid only partly matches its link to other Alzheimer's brain changes; this is an association study of post-mortem tissue, not a test of risk or 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.
- Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population
- A human iPSC model of Tauopathies engineered for 4R Tau isoform expression endogenously develops late‐stage neuronal Tau pathology
- The effects of chronic glucocorticoid exposure on dendritic length, synapse numbers and glial volume in animal models: implications for hippocampal volume reductions in depression
- MAPT splicing modulators reduce 4R tau and rescue tauopathy phenotypes in human neurons and in a mouse model
- Relation between apolipoprotein E genotype, hepatitis B virus status, and thyroid status in a sample of older persons with Down syndrome
- Insulin and the insulin receptor in experimental models of learning and memory
- Lipid-associated macrophages' promotion of fibrosis resolution during MASH regression requires TREM2
- p53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR)
- Inhibition of c-Jun N-terminal kinase activation reverses Alzheimer disease phenotypes in APPswe/PS1dE9 mice
- Dissection of blood-brain barrier dysfunction through CSF PDGFRβ and amyloid, tau, neuroinflammation, and synaptic CSF biomarkers in neurodegenerative disorders