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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An acquisition protocol using time windows of 0-30 and 120-140 min with appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy.
Why it matters
This study validated a shorter, two-window PET scanning protocol for measuring amyloid in the brain that agrees well with the full-length protocol while being more comfortable for patients. It is a methods study about imaging, not about treating or preventing Alzheimer's disease.
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Here we report that TREM2 deficiency leads to accelerated and exacerbated hyperphosphorylation and aggregation of tau in a humanized mouse model of tauopathy.
Why it matters
In a humanized mouse model of tauopathy, lacking TREM2 led to faster and worse hyperphosphorylation and aggregation of tau. This is animal work showing TREM2 helps limit tau pathology, not a treatment for people.
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52/100
We analyzed CSF concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) among 132 neurologically normal older adults (mean 64.5, range 55-85), along with bilateral hippocampal volumes and a measure of episodic memory (Auditory Verbal Learning Test, delayed recall).
Why it matters
This study examined whether cerebrospinal fluid neurogranin, a synaptic protein, is associated with memory in neurologically healthy older adults, independent of established Alzheimer biomarkers. It is an observational biomarker study and does not test any treatment, cure, or prevention.
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The cerebrospinal fluid (CSF) signature of reduced amyloid beta 1-42 (Aβ 42 ), elevated total tau (t-tau), and phosphorylated tau181 (p-tau) is important for the early diagnosis of Alzheimer's disease (AD).
Why it matters
Pooling sixteen articles with 590 Parkinson's patients with cognitive impairment and 1182 with normal cognition, this meta-analysis found lower spinal-fluid amyloid beta in the impaired group. In those with Parkinson's disease dementia, amyloid beta was lower and total tau and p-tau were higher, a pattern that is also important for diagnosing Alzheimer's disease. The authors suggest amyloid and tau changes may contribute to Parkinson's dementia, much as in Alzheimer's.
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52/100
Increasing evidence indicates that alterations of the cerebral microcirculation may play a role in Alzheimer disease, the leading cause of late-life dementia.
Why it matters
In mice, removing the brain's perivascular macrophages — immune cells that sit along blood-vessel walls where amyloid-β collects — "abrogates the reactive oxygen species production and cerebrovascular dysfunction induced by Aβ," including in Tg2576 mice that overproduce it. The authors tested whether these cells, via CD36 and Nox2, are the main source of that vessel-damaging oxidative stress. This is mechanistic animal research; it does not test a treatment or show any benefit for patients.
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Triggering Receptor Expressed on Myeloid cells 2 (TREM2), which is expressed on myeloid cells including microglia in the CNS, has recently been identified as a risk factor for Alzheimer's disease (AD).
Why it matters
In lab-grown microglia and in mice lacking the Trem2 gene, losing TREM2 reduced how well the brain's immune cells (microglia) survived and multiplied, stalled them at an early stage of cell division, and made β-catenin, a protein in the Wnt signalling pathway, less stable. The authors conclude that TREM2 supports microglial survival through this pathway. This was not a study in people and tested no treatment, so it does not show that targeting TREM2 or Wnt/β-catenin helps with Alzheimer's disease.
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52/100
FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls.
Why it matters
This study used FDG-PET to assess cerebral glucose metabolism in people newly diagnosed with Parkinson's disease and its association with cognitive decline over 18 months. It is about Parkinson's disease and cognition, not about treating, curing or preventing Alzheimer's disease.
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Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic and pathologic roles have not been well defined for this pathway.
Why it matters
In plasma astrocyte-derived exosomes, levels of BACE-1 and sAPPbeta were significantly higher and GDNF significantly lower in Alzheimer's disease patients than in controls, unlike in frontotemporal dementia patients. These findings describe possible biomarker differences but do not test or report any treatment, cure, or prevention.
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The prevalence of ICAS in older adults is high, and it could be a target for primary prevention of stroke and dementia in this population.
Why it matters
This study measured narrowing of brain arteries (intracranial atherosclerotic stenosis) in older adults and found it was common, with 31% having any and 9% having 50% or greater narrowing. Higher age, black race, higher systolic blood pressure and higher LDL cholesterol were linked to higher odds of this narrowing, but the study did not examine dementia or its treatment.
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Deposition of amyloid-β (Aβ) in the brain parenchyma and vessels is one of the hallmarks of Alzheimer disease (AD).
Why it matters
This study found that the dura mater can harbor amyloid-beta deposits, including in grafted dura mater from two cases. However, it suggests this seeding is unable to reproduce the full clinical and pathological picture of Alzheimer disease.
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Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous.
Why it matters
Mutations in VPS13C were found to cause an early-onset form of parkinsonism with rapid progression and early cognitive decline, and silencing VPS13C in cell models caused mitochondrial dysfunction and increased mitophagy. This is genetic and cell-model research into a parkinsonism-related condition, not a treatment or prevention for Alzheimer's disease.
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This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS-FTD disease continuum.
Why it matters
This study found that speech and pause measures during reading aloud differed between patient groups and healthy controls, and that an articulatory rate measure could distinguish bulbar ALS or FTD-PNFA from respiratory ALS or FTD-BV. The findings concern assessment and identification of oral-motor deficits, not treatment, cure, or prevention of dementia.
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52/100
Maintaining DNA integrity is vital for all cells and organisms.
Why it matters
This study found reduced levels of the DNA repair factor BRCA1 in Alzheimer's brains and in transgenic mice, and that knocking down BRCA1 in mice caused DNA damage, neuronal shrinkage, and synaptic plasticity impairments. It is early animal and tissue research and does not establish that targeting BRCA1 treats or prevents Alzheimer's disease in people.
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This is the first study to assess cerebral microinfarcts (CMIs) on 3 tesla (3T) magnetic resonance imaging (MRI) in a memory clinic population.
Why it matters
This study assessed cerebral microinfarcts on 3 tesla MRI in 238 memory clinic patients in Singapore. The available text does not report how these microinfarcts related to cognition or diagnosis.
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Clearing cellular debris after brain injury represents an important mechanism in regaining tissue homeostasis and promoting functional recovery.
Why it matters
In cell and animal models of ischemic stroke, reducing TREM2 in microglia — the brain's immune cells — "reduced microglial activation to an amoeboid phenotype and decreased the phagocytosis of injured neurons", and the title reports that TREM2 deficiency "exacerbates ischemic damage". The authors also report a "potential endogenous TREM2 ligand". This is stroke research in the lab, not an Alzheimer's study, and it does not test any treatment in people; its relevance here is as evidence on how TREM2 helps microglia clear damaged brain cells.
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The impact of inflammation suppressor pathways on Alzheimer's disease (AD) evolution remains poorly understood.
Why it matters
In this mouse study, crossing the APP/PS1 model of cerebral amyloidosis with Il10-deficient mice restricted cerebral amyloidosis, preserved synaptic integrity, and mitigated cognitive disturbance. The authors suggest that blocking the IL-10 anti-inflammatory response may be therapeutically relevant for Alzheimer disease, but this is animal and in vitro work and has not been shown to treat or prevent the disease in people.
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This human study is based on an established cohort of "SuperAgers," 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20-30 years younger.
Why it matters
People over 80 with exceptional memory had a thicker region of the anterior cingulate cortex and fewer Alzheimer-type tangles than average elderly people. This describes brain features associated with preserved memory and does not test any treatment or prevention.
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52/100
Frontotemporal lobar degeneration (FTLD) comprises two main classes of neurodegenerative diseases characterized by neuronal/glial proteinaceous inclusions (i.e., proteinopathies) including tauopathies (i.e., FTLD-Tau) and TDP-43 proteinopathies (i.e., FTLD-TDP) while other very rare forms of FTLD are known such as FTLD with FUS pathology (FTLD-FUS).
Why it matters
This review of frontotemporal lobar degeneration (FTLD) says the same underlying disease can appear as behavioural, language or motor syndromes, and that "current clinical criteria do not reliably predict underlying proteinopathies ante-mortem." The exception is hereditary FTLD: MAPT mutations are associated with FTLD-Tau, and GRN, C9orf72, VCP and TARDBP mutations with FTLD-TDP. It concerns FTLD, not Alzheimer's disease, and reports no treatment, cure or prevention.
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Expanded GGGGCC (G4C2) nucleotide repeats within the C9ORF72 gene are the most common genetic mutation associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Why it matters
In neuron cultures, live-cell imaging and transgenic flies, the arginine-rich dipeptide PR from C9ORF72 repeats was potently neurotoxic and formed nuclear aggregates, and such aggregates were found in human induced motor neurons and patient spinal cord. This is early laboratory and animal work on a toxic mechanism, not a treatment or cure.
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Recent genome-wide association studies linked variants in TREM2 to a strong increase in the odds of developing Alzheimer's disease.
Why it matters
Because a single copy of a TREM2 variant, "likely resulting in a loss of function", was linked to higher Alzheimer's risk, this study compared plaque-model mice (APPPS1-21) with one versus two working copies of the trem2 gene. It found "no significant difference in Aβ deposition" at 3 or 7 months of age; the title reports an altered microglial response to plaques, but this record does not describe that change. This is mouse work that tests no treatment, and the authors state that how TREM2 affects Alzheimer's risk was "currently unknown".
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The β-site APP cleaving enzymes 1 and 2 (BACE1 and BACE2) were initially identified as transmembrane aspartyl proteases cleaving the amyloid precursor protein (APP).
Why it matters
This review states that BACE1 is a major drug target because its cleavage of APP is the first step in making pathogenic amyloid beta, but notes BACE1 is also needed for myelination. It describes the current status of BACE research and does not report a working treatment.
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α-Synuclein species contained in PD-derived LB are pathogenic and have the capacity to initiate a PD-like pathological process, including intracellular and presynaptic accumulations of pathological α-synuclein in different brain areas and slowly progressive axon-initiated dopaminergic nigrostriatal neurodegeneration.
Why it matters
When Lewy body extracts from Parkinson's disease brains were injected into mice and monkeys, the animals developed progressive damage to the nigrostriatal system, while animals given non-Lewy-body fractions did not. This supports the idea that pathological alpha-synuclein can spread, but it is animal work and not a treatment for patients.
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Intronic expansion of a hexanucleotide GGGGCC repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene is the major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
Why it matters
In cell and neuron models, the C9ORF72 protein was found to regulate endosomal trafficking and autophagy, and patient motor neurons showed altered colocalization with Rab proteins. This is laboratory research into how a disease-linked gene works, not a treatment or prevention for patients.
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Prions are proteins that adopt alternative conformations, which become self-propagating.
Why it matters
This study found that brain homogenates from multiple system atrophy cases transmitted disease to transgenic mice, providing evidence that alpha-synuclein aggregates in those patients are prions. It is animal transmission research, so it does not yet show any treatment, cure or prevention for Alzheimer's disease.
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Neuroinflammation may be involved in the pathophysiology of Parkinson's disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment.
Why it matters
This study measured inflammatory markers in cerebrospinal fluid from 87 Parkinson's disease patients and 33 reference participants and looked for links to depression, fatigue and cognitive impairment. It concerns Parkinson's disease and does not report a treatment or cure for Alzheimer's disease.