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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The mechanisms by which trisomy 21 leads to the characteristic Down syndrome (DS) phenotype are unclear.
Why it matters
This study compared gene activity in adult brains of people with Down syndrome and controls, finding widespread changes but not increased activity of the APP gene. It identified other genes linked to APP processing that were changed, but these are observations and not a treatment or cure.
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Elevated beta-secretase (beta-site amyloid precursor protein-cleaving enzyme 1 [BACE1]) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls.
Why it matters
This study examined whether the enzyme BACE1 could be detected in the cerebrospinal fluid of patients with mild cognitive impairment, a group at high risk for Alzheimer's disease. It is a diagnostic question about measuring a protein in fluid, not a test of any treatment, cure, or prevention.
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Amyloid beta (Abeta) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer's disease to determine if intraneuronal Abeta immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration.
Why it matters
In post-mortem brains from 32 controls, 31 people with Down syndrome and 36 people with sporadic Alzheimer's disease, amyloid-beta staining inside neurons appeared already in infancy and stayed stable through adulthood and normal aging. It was strongest in brain areas *least* prone to plaques, tangles and neuron loss, and was mainly a shortened form (Abeta 17-40/42) that differs from the form found in plaques. The authors conclude this intraneuronal staining is not a predictor of plaques or tangles and may reflect normal neuron metabolism. This is a tissue study, not evidence about diagnosis or treatment.
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Amyloid plaque is the hallmark and primary cause of Alzheimer disease.
Why it matters
In this research, activating the beta2-adrenergic receptor increased gamma-secretase activity and amyloid-beta production, suggesting a possible pathway by which stress could promote plaque formation. This is early laboratory work, so it does not yet show that blocking this receptor prevents or treats Alzheimer's disease in people.
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There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism.
Why it matters
This review discusses how folate and vitamin B12 are involved in basic nervous system processes and notes they may have roles in preventing dementias including Alzheimer's disease. It does not report any trial result showing that taking these vitamins prevents or treats Alzheimer's disease.
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50/100
The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex.
Why it matters
In 76 people with CADASIL, an inherited small vessel disease causing stroke and subcortical vascular dementia, brain volume and its two-year change were linked to clinical scores. This identifies brain atrophy as an important part of the disease process in CADASIL, though this study is about CADASIL rather than Alzheimer's disease itself.
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Accumulation of amyloid-beta (Abeta) within extracellular spaces of the brain is a hallmark of Alzheimer disease (AD).
Why it matters
In mice bred without P-glycoprotein, a transporter on the blood vessels that line the brain, amyloid-beta injected into the brain was cleared at half the rate seen in normal mice. That fits the study's view that slower removal of amyloid-beta, rather than extra production, may help explain its build-up in late-onset Alzheimer's. This is animal research: it did not test any treatment, and it does not show that the same thing happens in people.
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Beta-secretase (BACE1) is the rate-limiting protease for the generation of the amyloid beta-peptide (Abeta) in Alzheimer disease.
Why it matters
In mice, removing the BACE1 gene almost completely blocked amyloid beta production in neurons but caused health problems and early death, while BACE2 removal appeared harmless. The findings suggest that BACE2 may also contribute to amyloid beta production in the brain, which raises questions about the safety of targeting BACE1 as a treatment.
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Alzheimer disease (AD) is characterized neuropathologically by intracellular neurofibrillary tangles (NFT) and of extracellular senile plaques (SP), the central core of which is amyloid beta-peptide (Abeta) derived from amyloid precursor protein (APP), a transmembrane protein.
Why it matters
In hippocampus tissue from Alzheimer's disease brains, the protein Pin1 was found to be significantly down-regulated and oxidized, a change the authors link to oxidative stress. This is a tissue analysis identifying a possible target of oxidation and does not show that correcting it treats or prevents the disease.
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The APOE*E4 genotype status appears to have a greater deleterious effect on gross hippocampal pathology and memory performance in women than in men.
Why it matters
In this study of people with mild cognitive impairment, women carrying one or two APOE*E4 alleles had significantly reduced hippocampal volume, while men showed this only with two alleles. It describes a risk-related pattern and offers no treatment, cure or prevention.
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50/100
Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.
Why it matters
In 511 older adults without dementia, higher diastolic blood pressure five years before an MRI scan went with a smaller hippocampus in people not treated for hypertension, while in people already on treatment it was *low* diastolic pressure that went with more atrophy. People with more white matter lesions also more often had severe shrinkage of the hippocampus and amygdala. This observational study shows associations only — the authors say blood pressure and small-vessel disease "may be associated" with atrophy in areas affected by Alzheimer pathology — and it did not test any treatment.
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NIFID is a neuropathologically distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that may include parkinsonism or MND.
Why it matters
This study describes the clinical and neuropathological features of 10 cases of neuronal intermediate filament inclusion disease, a distinct variant of frontotemporal dementia. It provides information about this rare disease but does not test any treatment, cure, or prevention.
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We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains.
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Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau.
Why it matters
This study demonstrates that tau is cleaved at D421 by executioner caspases, and that following caspase-cleavage, the truncated tau facilitates filament formation. This suggests caspase-cleavage of tau is an early event in Alzheimer's disease tangle pathology.
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Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (A beta peptides) in the brain.
Why it matters
In transgenic mice, overexpressing the alpha-secretase ADAM10 prevented amyloid plaque formation and hippocampal defects. This is animal research, so it is too early to know whether increasing ADAM10 activity would help people with Alzheimer's disease.
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Lewy bodies (LBs), which are the hallmark pathologic features of Parkinson's disease and of dementia with LBs, have several morphologic and molecular similarities to aggresomes.
Why it matters
In this cell study, aggresomes formed by alpha-synuclein and synphilin-1 were found in 60% of nonapoptotic cells but only 10% of apoptotic cells, indicating a disconnection between aggresome formation and apoptosis. The authors support a protective role for these inclusions from the toxicity associated with combined over-expression of alpha-synuclein and synphilin-1.
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Triggering receptors expressed by myeloid cells (TREMs) belong to a rapidly expanding family of receptors that include activating and inhibitory isoforms encoded by a gene cluster linked to the MHC.
Why it matters
This review describes TREM1 and TREM2 activating myeloid cells through DAP12, and notes that TREM2 deficiency causes bone cysts and central nervous system demyelination leading to dementia. It is a general review and does not report a treatment, cure or prevention.
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As there are no biological markers for the antemortem diagnosis of degenerative parkinsonian disorders, diagnosis currently relies upon the presence and progression of clinical features and confirmation depends on neuropathology.
Why it matters
This task force report reviews clinical diagnostic criteria for parkinsonian disorders and notes that without biological markers, diagnosis relies on clinical features and that misdiagnosis is common, especially early. It addresses diagnosis only and reports no treatment, cure, or prevention.
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The major protein constituent of Lewy bodies (LBs), the pathological hallmark of Parkinson disease and dementia with Lewy bodies, is considered to be alpha-synuclein, but other proteins, in particular the microtubule-associated protein tau, have been implicated in the pathogenesis of LBs.
Why it matters
Using multiple tau antibodies, this laboratory study found tau and alpha-synuclein together in Lewy bodies, suggesting the two proteins may clump together in the same neurons. It is a tissue-staining study only and does not test any treatment, cure or prevention.
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Two apolipoprotein E (apoE) receptors, the very low density lipoprotein (VLDL) receptor and apoE receptor 2 (apoER2), are also receptors for Reelin, a signaling protein that regulates neuronal migration during brain development.
Why it matters
In knockout mice, lacking the VLDL receptor or apoE receptor 2 caused deficits in fear conditioning and long-term potentiation, and Reelin enhanced long-term potentiation in normal hippocampal slices but not in these knockout mice. This suggests apoE receptors and Reelin are involved in synaptic plasticity and learning, but the findings are from animals and do not establish a treatment.
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Intracytoplasmic inclusions composed of alpha-synuclein (alpha-syn) are characteristic of neurodegenerative Lewy body disorders.
Why it matters
Using newly developed antibodies against altered alpha-synuclein, this 2002 brain-tissue study reported an "unprecedented and extensive" build-up of alpha-synuclein in the striatum (a movement-related brain region) in Lewy body diseases, densest in people with pure dementia with Lewy bodies or Alzheimer's combined with dementia with Lewy bodies. The authors suggest these deposits "may contribute" to the parkinsonism (stiffness, slowness) seen in these conditions; this is a proposed link, not a proven cause. It is a laboratory finding and tested no treatment.
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The purpose of this study is to explore the possibility of progressive neuropsychological decline in chronic temporal lobe epilepsy (TLE) and determine how this vulnerability may be associated with the neurodevelopmental impact of the disorder. 53 patients with TLE and 62 healthy controls underwent quantitative MRI volumetric imaging of total brain tissue and hippocampal volumes as well as assessment of intelligence and memory function.
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Fibrillar alpha-synuclein is a component of the Lewy body, the characteristic neuronal inclusion of the Parkinson's disease (PD) brain.
Why it matters
In laboratory membranes, protofibrillar alpha-synuclein bound tightly and briefly made vesicles leaky, unlike the monomeric or fibrillar forms. This suggests that an early clump form, not the mature fibril, may damage cells, but it is in-vitro work with no patient testing.
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Familial Danish dementia (FDD), also known as heredopathia ophthalmo-oto-encephalica, is an autosomal dominant disorder characterized by cataracts, deafness, progressive ataxia, and dementia.
Why it matters
In a Danish kindred with familial Danish dementia, a 10-nucleotide duplication in the BRI gene was found to originate an amyloid peptide, with neuropathological findings similar to Alzheimer's disease. This concerns a rare familial dementia and reports no treatment, cure or prevention for Alzheimer's disease.
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Alzheimer's disease (AD) is characterized by the presence of senile plaques, neurofibrillary tangles, and neuronal cell loss associated with membrane cholesterol release. 24S-hydroxycholesterol (24S-OH-Chol) is an enzymatically oxidized product of cholesterol mainly synthesized in the brain.
Why it matters
Plasma 24S-hydroxycholesterol was modestly but significantly higher in Alzheimer and vascular dementia patients than in healthy controls or depressed patients, with no significant difference between the two dementia groups. This suggests a possible biochemical marker related to brain cholesterol, but it is not a treatment or prevention and the authors describe it only as a putative marker.
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.
- Amyloid Precursor Protein (APP) Metabolites APP Intracellular Fragment (AICD), Aβ42, and Tau in Nuclear Roles
- Pattern of regional cortical thinning associated with cognitive deterioration in Parkinson's disease
- Language functions in Huntington's disease
- A combination of long- and short-read genomics reveals frequent p-arm breakpoints within chromosome 21 complex genomic rearrangements
- The complexity of neuroinflammation consequent to traumatic brain injury: from research evidence to potential treatments
- C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins
- TREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia
- Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism
- Cell-mediated neuroprotection in a mouse model of human tauopathy
- Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function