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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Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer's disease (AD) and some frontotemporal dementias.
Why it matters
This review argues that end-stage neurofibrillary lesions do not cause neuronal loss, but that alterations to soluble tau proteins, including aberrant tau phosphorylation, induce neurodegeneration. It comments on the tractability of altering phosphorylation-dependent tau functions for therapeutic intervention in Alzheimer's disease and related disorders, but reports no tested treatment.
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Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages.
Why it matters
This is a review of factors that regulate microglial activation, including TREM2. It reports no new treatment, cure, or prevention for Alzheimer's disease.
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PICALM, a clathrin adaptor protein, plays important roles in clathrin-mediated endocytosis in all cell types.
Why it matters
The PICALM protein was abnormally cleaved in Alzheimer's disease brains, with lower levels of the full-length form, and it was found attached to neurofibrillary tangles alongside abnormal tau. These findings suggest PICALM is associated with the development of tau pathology in Alzheimer's disease.
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Thirty patients with MCI and nonpathologic CSF total tau levels, nine patients with MCI and pathologic CSF total tau levels, and 16 age-matched healthy control subjects underwent diffusion-tensor imaging at baseline and after a mean follow-up of 2.6 years ± 0.54 (standard deviation), with range of 1.58-3.98 years.
Why it matters
This longitudinal study looked at whether pathologic cerebrospinal fluid total tau levels in patients with mild cognitive impairment were related to later changes in white matter integrity on imaging. It is observational and does not test any treatment or prevention.
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49/100
Abnormal deposition and intercellular propagation of α-synuclein plays a central role in the pathogenesis of disorders such as Parkinson's Disease (PD) and dementia with Lewy bodies (DLB).
Why it matters
In this study, antibodies against alpha-synuclein helped microglia clear extracellular alpha-synuclein and prevented its spread to neighboring cells, building on mouse immunization work. It concerns alpha-synuclein disorders such as Parkinson's disease and dementia with Lewy bodies, and reports no Alzheimer's treatment or outcome.
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Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions.
Why it matters
This review describes epidemiological links between low vitamin D and Alzheimer's disease, alongside preclinical findings that vitamin D can regulate catecholamine levels and protect against Alzheimer-like pathology. It highlights areas where future research should focus rather than reporting a treatment or prevention effect.
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The Framingham Heart Study has enrolled 3 generations of participants, the original cohort (gen 1) enrolled in 1948, the offspring cohort (gen 2) enrolled in 1971 and the third generation enrolled in 2002.
Why it matters
This article describes the Framingham Brain Donation Program and its neuropathology along the cognitive continuum. It does not test any treatment, cure, or prevention for Alzheimer's disease, and it is a description of a research resource.
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49/100
The lack of fibrillar β-amyloid (Aβ) as visualized by PiB PET in APParc mutation carriers suggests, given the reduced glucose metabolism and levels of Aβ(1-42) in CSF, that other forms of Aβ such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease.
Why it matters
Two carriers of the Arctic APP mutation had very low amyloid PET signal despite abnormal glucose metabolism and spinal fluid markers. This suggests that some inherited forms of Alzheimer disease may not show up on standard amyloid PET scans, which matters for diagnosis and for using such scans in trials.
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Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease thought to be caused, at least in part, by repetitive brain trauma, including concussive and subconcussive injuries.
Why it matters
This review describes chronic traumatic encephalopathy as a neurodegenerative disease thought to be caused at least in part by repetitive brain trauma, with hyperphosphorylated tau and TDP-43 accumulation. It is about CTE, not Alzheimer's disease, and does not report a treatment, cure, or prevention.
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Increasing evidence suggests a role of atherosclerosis in the pathogenesis of cognitive impairment and dementia.
Why it matters
This study investigated whether atherosclerotic calcification at four locations is associated with cognition and brain changes on MRI in non-demented people. It reports associations with vascular measures and brain imaging, so it does not establish a treatment, cure or prevention.
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Accumulation of the amyloid β (Aβ) peptide within the brain is hypothesized to be one of the main causes underlying the pathogenic events that occur in Alzheimer disease (AD).
Why it matters
In this laboratory study, increasing levels of the LDL receptor enhanced the uptake and clearance of amyloid-β by astrocytes, while deleting it decreased uptake, and this effect occurred without apolipoprotein E. These findings identify a possible pathway for clearing amyloid-β from the brain, but they are early laboratory work and do not show a treatment or prevention for Alzheimer's disease in people.
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There was complete agreement between visual reads of ¹⁸F-flutemetamol PET scans (3 blinded readers with majority rule) and histology.
Why it matters
In seven patients who had a prior cortical biopsy, visual reads of flutemetamol PET scans agreed completely with histology for amyloid plaques. This concerns validation of an imaging method, not treating, curing or preventing Alzheimer disease.
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A clinically and pathologically heterogeneous type of frontotemporal lobar degeneration has abnormal tau pathology in neurons and glia (FTLD-tau).
Why it matters
This review describes the pathology of frontotemporal lobar degeneration with tau, noting that diagnosis currently rests on postmortem brain examination. 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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Consistent with neuropathological findings from postmortem studies, [(18)F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group.
Why it matters
This small cross-sectional study found higher brain binding of a PET tracer in adults with Down syndrome than in controls, and higher binding in some brain regions than in people with Alzheimer disease. It does not show whether this tracer signal predicts later dementia, and it offers no treatment or prevention.
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The past 25 years have seen a major expansion of knowledge concerning the cause of Parkinson's disease provided by an understanding of environmental and genetic factors that underlie the loss of nigral dopaminergic neurons.
Why it matters
This review states that mitochondrial dysfunction, oxidative stress, altered protein handling and inflammation are thought to lead to cell dysfunction and death in Parkinson's disease, with ageing the most important risk factor. It discusses possible targets for neuroprotection but reports no treatment or cure.
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The goal of this study was to investigate the role of endogenous amyloid-β peptide (Aβ) in healthy brain.
Why it matters
Reducing endogenous amyloid-beta in mouse hippocampal slices and in mice impaired synaptic plasticity and memory, suggesting this peptide has a normal role in healthy brain function. This is animal and laboratory research, so it does not directly show how to treat or prevent Alzheimer's disease in people.
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49/100
No frontal cognitive effects were as robust as memory decline.
Why it matters
In this longitudinal study, APOE ε4 carriers showed faster decline on a memory test but not on frontal tests, while ε4 homozygotes declined faster on some mental arithmetic tests. It describes cognitive changes linked to APOE ε4 and offers no treatment or prevention.
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Chronic traumatic encephalopathy (CTE) is a form of neurodegeneration believed to result from repeated head injuries.
Why it matters
This review describes chronic traumatic encephalopathy (CTE), a brain disease believed — not proven — to follow repeated blows to the head. First described in 15 retired boxers, it has since been reported after American football, hockey, soccer, professional wrestling and physical abuse. The authors list its brain changes (shrinkage, tau tangles, sometimes TDP-43 protein) and the problems seen alongside them: memory and planning trouble, mood and personality changes including depression and suicidality, and parkinsonism. When it was written there were no formal criteria for diagnosing CTE, and it reports no data on how common CTE is or who will develop it.
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The activation and fusion of macrophages and of osteoclasts require the adaptor molecule DNAX-activating protein of 12 kD (DAP12), which contains immunoreceptor tyrosine-based activation motifs (ITAMs).
Why it matters
This study describes how TREM2 and DAP12 activate PI3K signaling in osteoclasts, and notes that loss of TREM2 causes Nasu-Hakola disease with bone cysts and dementia. It is basic cell signaling work, not an Alzheimer's treatment.
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Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients.
Why it matters
This study sequenced the CHMP2B gene in 433 ALS cases and found 4 cases carrying 3 missense mutations, following earlier reports of CHMP2B mutations in a family with frontotemporal dementia and in two familial ALS patients. It concerns ALS and frontotemporal dementia genetics, not the treatment, cure or prevention of Alzheimer's disease.
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In 2006, TAR DNA-binding protein 43 (TDP-43), a highly conserved nuclear protein, was identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and in the most common variant of frontotemporal lobar degeneration (FTLD), FTLD-U, which is characterized by cytoplasmic inclusions that stain positive for ubiquitin but negative for tau and alpha-synuclein.
Why it matters
This review summarizes evidence that TDP-43 is the major disease protein in ALS and FTLD-TDP and that these represent two ends of a spectrum of TDP-43 proteinopathies. It discusses opportunities for better diagnostics and disease-modifying therapies but reports no treatment or cure itself.
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49/100
Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth.
Why it matters
This review suggests that regular exercise may protect against conditions including dementia, partly through anti-inflammatory effects mediated by muscle-derived myokines. These are proposed mechanisms, and the review does not show that exercise treats or prevents Alzheimer's disease.
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Neuropathology involving TAR DNA binding protein-43 (TDP-43) has been identified in a wide spectrum of neurodegenerative diseases collectively named as TDP-43 proteinopathy, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD).
Why it matters
This study used fruit flies to show that increased expression of human TDP-43 caused progressive neurodegeneration in the fly eye and brain. It is an animal model, so it does not establish a treatment or prevention for people.
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Although Parkinson disease (PD) is viewed traditionally as a motor syndrome secondary to nigrostriatal dopaminergic denervation, recent studies emphasize non-motor features.
Why it matters
This review describes evidence that degeneration of the basal forebrain cholinergic system appears early in Parkinson disease and worsens with dementia, with cholinergic loss in parkinsonian dementia similar to or more severe than in Alzheimer disease. It is a review of disease mechanisms and reports no treatment or cure.
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FUS gene mutations were recently identified in familial amyotrophic lateral sclerosis (ALS).
Why it matters
FUS mutations were found in 3.2% of familial ALS cases in this genetic screening, making them a relatively uncommon cause. This concerns ALS genetics and does not address treating, curing or preventing Alzheimer's disease.
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.
- Regulated formation of Golgi secretory vesicles containing Alzheimer beta-amyloid precursor protein
- Aducanumab-Related Amyloid-Related Imaging Abnormalities: Paean or Lament?
- Long-term accumulation of amyloid-beta in axons following brain trauma without persistent upregulation of amyloid precursor protein genes
- Exome sequencing reveals VCP mutations as a cause of familial ALS
- Transmission of multiple system atrophy prions to transgenic mice
- α-synuclein and tau: interactions, cross-seeding, and the redefinition of synucleinopathies as complex proteinopathies
- Chronic elevation of S100 beta protein does not alter APP mRNA expression or promote beta-amyloid deposition in the brains of aging transgenic mice
- Levels of beta-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment
- Advanced glycation end-products disrupt the blood-brain barrier by stimulating the release of transforming growth factor-β by pericytes and vascular endothelial growth factor and matrix metalloproteinase-2 by endothelial cells in vitro
- Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease