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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Intracytoplasmic aggregation of alpha-synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson's disease, whereas if this process also occurs in the cortical neurons, it is considered pathognomonic for dementia with Lewy bodies.
Why it matters
Researchers selected autopsy cases purely because their brains contained alpha-synuclein deposits (the protein that forms Lewy bodies), regardless of symptoms in life. Looking back at clinical records, only 32 of 106 such cases (30%) had been diagnosed with a neurodegenerative disorder. The amount or location of the deposits did not dependably indicate whether a person had movement symptoms or cognitive impairment. Because some people with no neurological impairment had "a reasonable burden" of these deposits, the study concludes they are "not definite markers of neuronal dysfunction".
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The E693Q mutation in the amyloid beta precursor protein (APP) leads to cerebral amyloid angiopathy (CAA), with recurrent cerebral hemorrhagic strokes and dementia.
Why it matters
In mice overexpressing human E693Q APP, amyloid was directed to blood vessels, causing cerebral amyloid angiopathy, smooth muscle cell degeneration, hemorrhages, and neuroinflammation. This is an animal model of hereditary cerebral hemorrhage with amyloidosis-Dutch type, not a treatment, cure, or prevention for Alzheimer's disease.
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We have previously shown that apolipoprotein E (Apoe) promotes the formation of amyloid in brain and that astrocyte-specific expression of APOE markedly affects the deposition of amyloid-beta peptides (Abeta) in a mouse model of Alzheimer disease.
Why it matters
In dishes of brain tissue containing amyloid plaques, astrocytes (brain support cells) from normal mice broke down the deposited amyloid-beta, but astrocytes from mice lacking apolipoprotein E did not, and they took up less of the deposits. Blocking apoE, amyloid-beta, or the LDL-receptor family of receptors also stopped the breakdown, so the authors conclude apoE "seems to be important" for astrocytes to clear deposited amyloid, a process they suggest "may be impaired in Alzheimer disease." This was a laboratory mouse-cell study with no reported effect sizes; it did not test APOE variants, people, or any treatment.
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New hippocampal neurons are continuously generated in the adult brain.
Why it matters
In rats, lipopolysaccharide-induced inflammation with microglia activation strongly impaired basal hippocampal neurogenesis, and this impairment was restored by minocycline, which inhibits microglia. These are animal findings and do not establish a treatment, cure or prevention for Alzheimer's disease in people.
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52/100
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), Nasu-Hakola disease, is a globally distributed recessively inherited disease.
Why it matters
This study reports that a lack of DAP12 or TREM2 "results in impaired osteoclast differentiation and osteoporotic features", which concerns the cells that break down bone. It builds on the authors' earlier finding that mutations in these two genes cause Nasu-Hakola disease (PLOSL), an inherited disease with bone cysts, fractures, white-matter loss and "profound presenile dementia". The record does not mention Alzheimer's disease, gives no methods or numbers, and reports no treatment.
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Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-beta (Abeta), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain.
Why it matters
In mice and rats, raising serum insulin-like growth factor I reduced brain amyloid-beta, while low levels were linked to higher amyloid-beta. This is animal research, and the authors describe circulating IGF-I as having therapeutic potential, not as a proven treatment for people.
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52/100
The amygdala exhibits significant pathological changes in Parkinson's disease, including atrophy and Lewy body (LB) formation.
Why it matters
This study found that the amygdala shows Lewy body formation in Parkinson's disease, and that more Lewy body-containing neurons in one nucleus were linked to visual hallucinations. 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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The authors studied the accuracy of clinical diagnosis of idiopathic PD (IPD) in 100 consecutive clinically diagnosed cases that came to neuropathological examination.
Why it matters
Checking brain tissue from 100 people diagnosed in life with Parkinson's disease, this study found 90 had the expected pathology and 10 had other diseases. It suggests that even the best current clinical criteria may misdiagnose about one in ten cases, which matters for research and treatment decisions.
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Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distribution and impaired antigen presentation capacity of dendritic cells (DCs).
Why it matters
In human immune cells grown from blood monocytes (dendritic cells), this 2001 lab study reports that TREM-2 is a surface receptor that works through the adaptor DAP12. Triggering it raised the receptor CCR7, produced "partial DC maturation" and helped the cells survive, using a signalling route the authors say differs from Toll-like receptors. It is basic immunology. It does not study the brain, microglia or people with Alzheimer's, and it reports no numbers.
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Several mutations in the amyloid precursor protein (APP) gene have been found to associate with pathologic deposition of the beta-amyloid peptide (Abeta) in neuritic plaques or in the walls of cerebral vessels.
Why it matters
This study reports a novel amyloid precursor protein mutation in a three-generation Iowa family with autosomal dominant dementia beginning in the sixth or seventh decade of life. Neuropathological examination revealed severe cerebral amyloid angiopathy, widespread neurofibrillary tangles, and unusually extensive distribution of Abeta40 in plaques.
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Endocytosis is critical to the function and fate of molecules important to Alzheimer's disease (AD) etiology, including the beta protein precursor (betaPP), amyloid beta (Abeta) peptide, and apolipoprotein E (ApoE).
Why it matters
In brain tissue, neurons in sporadic Alzheimer's disease showed enlarged early endosomes, the compartments cells use to take in and recycle material. The change appeared before amyloid deposits had spread beyond the entorhinal region, was more pronounced in APOE ε4 carriers, and was seen in some neurons in Down syndrome as early as 28 weeks of gestation. The authors call it "the earliest known intraneuronal change" in sporadic AD (as of 2000), but endosomes were normal in familial AD caused by presenilin mutations, the record gives no case numbers, and the study tests no treatment or prevention.
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Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon4 > epsilon3) for Alzheimer's disease (AD).
Why it matters
In amyloid-forming mice, those lacking apoE still built up amyloid but neuritic degeneration was virtually absent, and mice expressing human apoE4 had more than 10-fold more fibrillar deposits. The authors conclude apoE plays a critical, isoform-specific role in neuritic plaque formation.
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Why it matters
Reports the purification and cloning of amyloid precursor protein beta-secretase from human brain.
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52/100
The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17.
Why it matters
In one family with a P301S mutation in the tau gene, a father developed frontotemporal dementia and his son corticobasal degeneration, both "rapidly progressive" and starting in their twenties, showing that "the same primary gene defect in tau can lead to 2 distinct clinical phenotypes." The father's brain showed "extensive filamentous pathology made of hyperphosphorylated tau protein," and in lab tests the mutant tau protein had "a greatly reduced ability to promote microtubule assembly." This is a two-person family report about a tau-related dementia, not Alzheimer's disease, and it tests no treatment.
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Familial British dementia (FBD), previously designated familial cerebral amyloid angiopathy-British type, is an autosomal dominant disorder of undetermined origin characterized by progressive dementia, spasticity, and cerebellar ataxia, with onset at around the fifth decade of life.
Why it matters
This study identified a protein called ABri in amyloid fibrils from people with familial British dementia, a rare inherited disorder that is not Alzheimer's disease. It links a mutation in the BRI gene on chromosome 13 to this condition, but does not show how to treat, cure, or prevent Alzheimer's disease.
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Down syndrome (DS) is a major cause of mental retardation and congenital heart disease.
Why it matters
This study used cell lines from people with partial trisomy 21 to build a phenotypic map assigning regions of chromosome 21 to features of Down syndrome, including an Alzheimer-like dementia. It is genetic mapping work and reports no treatment, cure or prevention.
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Severe, and often fatal, neuroleptic sensitivity may occur in elderly patients with confusion, dementia, or behavioural disturbance.
Why it matters
In this retrospective study, most patients with Lewy body type dementia who received neuroleptics had adverse reactions, often severe, and severe sensitivity was associated with increased mortality in the following year. This is a warning about neuroleptic sensitivity in Lewy body dementia, not a treatment, cure, or prevention for Alzheimer's disease.
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Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV).
Why it matters
This commentary discusses toxoplasmic encephalitis in AIDS, which can cause dementia-like symptoms, but it is not about Alzheimer's disease. It does not address Alzheimer's disease treatment, cure, or prevention.
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The principal component of amyloid plaques in Alzheimer disease is beta-amyloid protein, an approximately 4-kDa peptide derived from amyloid precursor proteins.
Why it matters
In cultured cells, this study found that amyloid precursor protein is cleaved on the plasma membrane by a membrane-bound protease. It describes a basic mechanism of APP processing but does not test any treatment or prevention.
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The researchers determined the sequences of human tau protein isoforms that feature amino-terminal insertions.
Why it matters
Reports the sequences of several forms (isoforms) of the human protein tau and where they are found in the neurofibrillary tangles of Alzheimer's disease.
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In DS, longitudinal characterization of all previously identified proteins revealed distinct trajectories over time and an association of baseline levels with future cognitive decline.
Why it matters
In 59 adults with Down syndrome, baseline blood protein levels were associated with later cognitive decline, but after correction for multiple comparisons no longitudinal protein changes were significantly related to changes in cognitive subdomain performance. This is a small observational study and offers no treatment or prevention.
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Considerable data support the presence of both systemic and CNS inflammation in SVD and VCID.
Why it matters
This review states that inflammation is present in cerebral small vessel disease and vascular cognitive impairment, but whether it causes these conditions is unclear. It calls for more longitudinal and interventional studies, so no treatment or prevention is established.
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Using human stem cell-derived neurons, we show that TDP-43 reduction induces cryptic splicing and downregulation of these genes, resulting in impaired excitability and synaptic transmission.
Why it matters
In human stem cell-derived neurons, reducing TDP-43 caused abnormal splicing and lowered levels of genes needed for nerve signaling, which impaired electrical excitability and synaptic transmission. Blocking these splicing events with antisense oligonucleotides partially restored neuronal function, and targeting several at once almost fully rescued the synaptic deficit, suggesting this process directly drives neuronal dysfunction in ALS and FTD.
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Among 203 enrolled patients, 186 (mean [SD] age, 68.7 [5.2] years; 119 males [64.0%]) were randomized (137 to the CN-105 group, 49 to the placebo group) and underwent surgery.
Why it matters
In this phase 2 randomized trial of older surgical patients, the drug CN-105 did not significantly reduce postoperative delirium compared to placebo. The study was small and preliminary, and the results do not support CN-105 as an effective treatment for delirium in this population.
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Elevated blood levels of phosphorylated tau (p-tau) are diagnostic of Alzheimer disease and are associated with the deposition of amyloid-β in the cerebral neuropil.
Why it matters
This study found higher levels of serum p-tau181 in people with AL and ATTR amyloidosis than in controls, suggesting blood p-tau can be raised by amyloid outside the brain. It does not test any treatment, cure or prevention of 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.
- The role of microglia and macrophages in the pathophysiology of the CNS
- Beneficial Metabolic Effects of TREM2 in Obesity Are Uncoupled From Its Expression on Macrophages
- Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis
- Long-term running exercise improves cognitive function and promotes microglial glucose metabolism and morphological plasticity in the hippocampus of APP/PS1 mice
- Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs
- Brain delivery of a neurotrophic peptide derived from secreted amyloid precursor protein APPsα as a therapeutic strategy for Alzheimer's disease
- Artificial intelligence in neuropathology: deep learning-based assessment of tauopathy
- Alpha 1-antichymotrypsin binding to Alzheimer A beta peptides is sequence specific and induces fibril disaggregation in vitro
- Basal forebrain cholinergic system in the dementias: Vulnerability, resilience, and resistance
- The frontotemporal dementia mutation R406W blocks tau's interaction with the membrane in an annexin A2-dependent manner