Apoptotic cell fragments locally activate tingible body macrophages in the germinal center.

Germinal centers (GCs) that form within lymphoid follicles during antibody responses are sites of massive cell death. Tingible body macrophages (TBMs) are tasked with apoptotic cell clearance to prevent secondary necrosis and autoimmune activation by intracellular self antigens. We show by multiple redundant and complementary methods that TBMs derive from a lymph node-resident, CD169-lineage, CSF1R-blockade-resistant precursor that is prepositioned in the follicle. Non-migratory TBMs use cytoplasmic processes to chase and capture migrating dead cell fragments using a "lazy" search strategy. Follicular macrophages activated by the presence of nearby apoptotic cells can mature into TBMs in the absence of GCs. Single-cell transcriptomics identified a TBM cell cluster in immunized lymph nodes which upregulated genes involved in apoptotic cell clearance. Thus, apoptotic B cells in early GCs trigger activation and maturation of follicular macrophages into classical TBMs to clear apoptotic debris and prevent antibody-mediated autoimmune diseases.

Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.

Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases.

ENTRAIN: integrating trajectory inference and gene regulatory networks with spatial data to co-localize the receptor-ligand interactions that specify cell fate.

MOTIVATION: Cell fate is commonly studied by profiling the gene expression of single cells to infer developmental trajectories based on expression similarity, RNA velocity, or statistical mechanical properties. However, current approaches do not recover microenvironmental signals from the cellular niche that drive a differentiation trajectory. RESULTS: We resolve this with environment-aware trajectory inference (ENTRAIN), a computational method that integrates trajectory inference methods with ligand-receptor pair gene regulatory networks to identify extracellular signals and evaluate their relative contribution towards a differentiation trajectory. The output from ENTRAIN can be superimposed on spatial data to co-localize cells and molecules in space and time to map cell fate potentials to cell-cell interactions. We validate and benchmark our approach on single-cell bone marrow and spatially resolved embryonic neurogenesis datasets to identify known and novel environmental drivers of cellular differentiation. AVAILABILITY AND IMPLEMENTATION: ENTRAIN is available as a public package at https://github.com/theimagelab/entrain and can be used on both single-cell and spatially resolved datasets.

Bioactivity evaluation and active compounds identification of Symphoricarpos orbiculatus as potential botanical herbicide.

BACKGROUND: Evaluation of herbicidal activity and identification of active compounds are important bases for the development of new botanical herbicides. RESULTS: This study confirmed that Symphoricarpos orbiculatus has high herbicidal activities against mono-dicotyledonous weeds, including Echinochloa crusgalli, Digitaria sanguinalis, Amaranthus retroflexus and Portulaca oleracea. By bioassay-guided isolation, 12 compounds were isolated and identified from S. orbiculatus for the first time, including iridoids: naucledal (K1), loganin (K2), loganigenin (K3), loganin acid (K4), glucologanin (K5) and vogeloside (K6), as well as flavonoids: quercetine (K7), luteolin (K8), nobiletin (K9), astragalin (K10), isorhamnetin 3-d-glucoside (K11) and rutin (K12). Biological assays showed that iridoids are the main active ingredients of S. orbiculatus. The compounds of K5 and K6 could inhibit both the root (IC50 = 37.54 and 38.91 µg mL-1, respectively) and shoot (IC50 = 42.78 and 45.72 µg mL-1, respectively) of Portulaca oleracea, which have a weeding toxicity similar to that of the commercialized plant-based herbicide pelargonic acid. In addition, the results of pot culture assay showed that S. orbiculatus ethanol extracts had high fresh weight control effect against Digitaria sanguinalis and P. oleracea at the concentration of 40 g L-1. After 7 days, both the soil treatment and the stem and leaf spray method resulted in severe leaf necrosis and significant leaf etiolation. CONCLUSION: Symphoricarpos orbiculatus and its herbicidal active compounds have the potential to develop into botanical herbicides, and are first reported in the present study. © 2024 Society of Chemical Industry.

Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19.

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. A novel population of naïve interferon-activated T cells is expanded in acute COVID-19 and is recruited into the memory compartment during convalescence in adults but not children. This was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

Distribution and identification of main Viruses Infecting Pepper in Qinghai.

From 2019 to 2021, pepper viruses were investigated in pepper planting areas and collected a total of 333 samples were in Qinghai (The central district, Datong, Huangzhong in Xining; Ledu district, Pingan, Huzhu, Minhe in Haidong, and Jianzha in Huangnan). RT-PCR and molecular cloning were conducted for virus detection in 333 suspected viral samples, the results revealed that viruses infecting pepper mainly included 11 capsicum viruses. Tomato spotted wilt tospovirus （TSWV）has the highest detection rate (36%) in Datong County, and Pepper cryptic virus 1 (PCV1) has the highest detection rate (57%) in Huangzhong County. In the Haidong, 86.3% of the peppers were Broad bean wilt virus 2（BBWV2）, virus-infected Pepper cryptic virus 2 (PCV2), TSWV and Cucumber mosaic virus （CMV） were detected in Xunhua, among which PCV1 and CMV had the highest detection rate (30.4%); PCV1, TSWV, and PCV2 were detected in Ledu and PCV2 had the highest detection rate (50%). There were 17 kinds of co-infection and the co-infection of two viruses occurred often. There were only 5 kinds of co-infection of three. Combined infection contained PCV1 and TMV was the most common. The distribution and species of pepper viruses from the pepper planting areas were clarified and it laid the foundation for preventing and controlling pepper viruses across Qinghai province.

Gene expression predicts dormant metastatic breast cancer cell phenotype.

BACKGROUND: Breast cancer can recur months to decades after an initial diagnosis and treatment. The mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and thus benefit from more rigorous screening and treatments. Unfortunately, the extreme rarity of dormant DTCs has been a major obstacle to their study. METHODS: To overcome this challenge, we developed an efficient system to isolate and study rare dormant breast cancer cells from metastatic organs including bones, which represent a major site of metastasis. After isolation of cells from the long bones, we used single cell RNA-sequencing (scRNA-seq) to profile proliferative and dormant PyMT-Bo1 breast cancer cells. We also compared this signature to dormant versus proliferative tumor cells isolated from the lungs. Finally, we compared our dormant signature to human datasets. RESULTS: We identified a group of genes including Cfh, Gas6, Mme and Ogn that were highly expressed in dormant breast cancer cells present in the bone and lung. Expression of these genes had no impact on dormancy in murine models, but their expression correlated with disease-free survival in primary human breast cancer tumors, suggesting that these genes have predictive value in determining which patients are likely to recur. CONCLUSIONS: Dormant breast cancer cells exhibit a distinct gene expression signature regardless of metastatic site. Genes enriched in dormant breast cancer cells correlate with recurrence-free survival in breast cancer patients.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone.

The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor-intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor-intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long-term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor-intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone-metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune-based therapies in solid cancers.

Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

A niche-dependent myeloid transcriptome signature defines dormant myeloma cells.

The era of targeted therapies has seen significant improvements in depth of response, progression-free survival, and overall survival for patients with multiple myeloma. Despite these improvements in clinical outcome, patients inevitably relapse and require further treatment. Drug-resistant dormant myeloma cells that reside in specific niches within the skeleton are considered a basis of disease relapse but remain elusive and difficult to study. Here, we developed a method to sequence the transcriptome of individual dormant myeloma cells from the bones of tumor-bearing mice. Our analyses show that dormant myeloma cells express a distinct transcriptome signature enriched for immune genes and, unexpectedly, genes associated with myeloid cell differentiation. These genes were switched on by coculture with osteoblastic cells. Targeting AXL, a gene highly expressed by dormant cells, using small-molecule inhibitors released cells from dormancy and promoted their proliferation. Analysis of the expression of AXL and coregulated genes in human cohorts showed that healthy human controls and patients with monoclonal gammopathy of uncertain significance expressed higher levels of the dormancy signature genes than patients with multiple myeloma. Furthermore, in patients with multiple myeloma, the expression of this myeloid transcriptome signature translated into a twofold increase in overall survival, indicating that this dormancy signature may be a marker of disease progression. Thus, engagement of myeloma cells with the osteoblastic niche induces expression of a suite of myeloid genes that predicts disease progression and that comprises potential drug targets to eradicate dormant myeloma cells.

Effects of RNAi-mediated plasma membrane calcium transporting ATPase and inositol 1,4,5-trisphosphate receptor gene silencing on the susceptibility of Mythimna separata to wilforine.

Wilforine, a compound of sesquiterpene alkaloids isolated from Tripterygium wilfordii, exhibits excellent insecticidal activity against Mythimna separata. In order to clarify the action mechanism of wilforine, the plasma membrane calcium transporting ATPase (PMCA) and inositol 1,4,5-trisphosphate receptor (IP3R) from M. separata were studied. Results showed that the open reading frame of MsIP3R and MsPMCA were 8118 bp and 3438 bp in length, as well as encoded 2706 and 1146 amino acids, respectively. Multiple sequence alignment and phylogenetic analysis revealed that the MsIP3R and MsPMCA had high homology with the IP3R and PMCA of other insects, but had low similarity with those of mammals, which means the IP3R and PMCA have potential to be the novel targets of insecticides with high selectivity between mammals and insects. Both MsIP3R and MsPMCA genes existed throughout the life cycle of M. separata, and were all predominantly expressed in somatic muscle of fifth-instar larvae and the adults. The susceptibilities of PMCA-silenced M. separata to wilforine were significantly lower than that of the normal M. separata, which illustrates that PMCA could be one of the targets of wilforine. However, the susceptibilities of IP3R-silenced M. separata to wilforine did not change significantly compared with the susceptibilities of normal M. separata, which shows that wilforine may not interact with the IP3R protein. These findings provide clues for elucidating the insecticidal mechanism of wilforine.

Comparative Performance and Neuropathologic Validation of the AD8 Dementia Screening Instrument.

BACKGROUND/OBJECTIVE: The AD8 informant-based screening instrument has been validated with molecular biomarkers of Alzheimer disease (AD) but not with the gold standard of neuropathologic AD. The objective of this study was to validate the AD8 with neuropathologic AD and compare its predictive performance with that of the Mini-Mental State Examination and both participant-derived and informant-derived subjective memory complaint (SMC) regarding the participant. METHODS: This longitudinal cohort study at the Knight Alzheimer Disease Research Center at Washington University included 230 participants, ages 50 to 91 years, who later had a neuropathologic examination. Four dementia screening instruments from their baseline assessment were evaluated: the AD8, Mini-Mental State Examination, participant SMC, and informant SMC. The primary outcome was a neuropathologic diagnosis of AD. RESULTS: The average participant age at baseline was 80.4 years, 48% were female. All 4 dementia screening tests were predictive of neuropathologic AD. There was no significant difference in the predictive performance of the AD8 compared with the other instruments, but the AD8 had superior sensitivity and combined positive and negative predictive values. CONCLUSION: The AD8 is a brief and sensitive screening instrument that may facilitate earlier and more accurate AD diagnosis in a variety of care settings.

Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease.

INTRODUCTION: The relationships between Alzheimer disease (AD), cognitive performance, and depression are poorly understood. It is unclear whether depressive features are a prodrome of AD. In addition, some studies of aging exclude depressed individuals, which may inappropriately limit generalizability. The aim of the present study was to determine whether depressive symptoms affect cognitive function in the context of preclinical AD. METHODS: Cross-sectional multivariate analysis of participants in a longitudinal study of aging (n=356) that evaluates the influence of depressive symptoms on cognitive function in cognitively normal adults. RESULTS: There is no relationship between the presence of depressive symptoms and cognitive function in those with either no evidence of preclinical AD or biomarker evidence of early-stage preclinical AD. However, in later stages of preclinical AD, the presence of depressive symptoms demonstrated interactive effects, including in episodic memory (0.96; 95% confidence interval, 0.31-1.62) and global cognitive function (0.46; 95% confidence interval, 0.028-0.89). CONCLUSIONS: The presence of depressive symptoms may be a late prodrome of AD. In addition, studies investigating cognitive function in older adults may not need to exclude participants with depressive symptomology, but may still consider depressive symptoms as a potential confounder in the context of more extensive neuronal injury.

Residue, dissipation, and safety evaluation of etoxazole and pyridaben in Goji berry under open-field conditions in the China's Qinghai-Tibet Plateau.

The dissipation and residual levels of etoxazole and pyridaben in Goji berry under open field conditions were determined by using GC-NPD (gas chromatography with nitrogen and phosphorus detector) with modified QuEChERS method. At fortification levels of 0.01, 1, and 5 mg/kg in Goji berry, it was shown that recoveries were ranged from 80.40 to 100.9% with relative standard deviation of the method (RSD) for repeatability ranged from 2.20 to 4.25%. The limit of quantification (LOQ) of the method was 0.01 mg/kg. The dissipation rates of etoxazole and pyridaben were described by using first-order kinetics and its half-life, as they are 7.13 days, 5.77 days, and 5.99 days (etoxazole) and 1.02 day, 0.67 day, 1.02 day (pyridaben). The terminal residues of etoxazole and pyridaben were below the European maximum residue limit (MRL, 0.1 mg/kg) in Goji berry when measured 7 days after the final application, which suggested that the use of these insecticides was safe for humans. This study would help in providing the basic information for developing regulation to guard a safe use of etoxazole and pyridaben in Goji berry and prevent health problem from consumers.

Prognostic impact of absolute lymphocyte count/absolute monocyte count ratio and prognostic score in patients with nasal-type, extranodal natural killer/T-cell lymphoma.

Nasal-type, extranodal natural killer/T-cell lymphoma is a heterogeneous disorder with poor prognosis, requiring risk stratification in this population. The combined value of baseline absolute lymphocyte count and absolute monocyte count provided prognostic information in some malignancies. However, the evidence requires validation in extranodal natural killer/T-cell lymphoma. Aiming to investigate the prognostic significance of absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score for extranodal natural killer/T-cell lymphoma, a retrospective research was carried out. A total of 264 patients with newly diagnosed extranodal natural killer/T-cell lymphoma were analyzed in this study. The patients' absolute lymphocyte count and absolute monocyte count tested at initial diagnosis were collected. Receiver operating curve analysis showed that the optimal cut-off values for absolute lymphocyte count and absolute monocyte count were 1.0 × 109 and 0.5 × 109L-1, respectively, and for absolute lymphocyte count/absolute monocyte count ratio was 2.85. After a median follow-up of 27 months (range 1-87 months), the 3-year overall survival and progression-free survival was 75.4% and 67.6%, respectively. Patients with absolute lymphocyte count/absolute monocyte count ratio ≥ 2.85 had better 3-year overall survival and progression-free survival than those with absolute lymphocyte count/absolute monocyte count ratio <2.85 (p < 0.001). According to absolute lymphocyte count/absolute monocyte count prognostic score, significant difference has been noticed in 3-year overall survival and progression-free survival (p < 0.001) and high absolute lymphocyte count/absolute monocyte count prognostic score was associated with poorer survival. The International Prognostic Index and Korean Prognostic Index were used for prognosis and showed no significant difference. When adding absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score to the International Prognostic Index and Korean Prognostic Index model, additional prognostic information was found. These results suggest that absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score might be useful prognostic factors in extranodal natural killer/T-cell lymphoma.

Serum B-cell activating factor predicts prognosis in nasal type, extranodal NK/T cell lymphoma.

B-cell activating factor (BAFF) plays important roles in a variety of lymphoid malignancies. Compared with healthy adults, patients with non-Hodgkin lymphoma had higher level of serum BAFF, and it corresponded with disease severity, response for therapy and clinical outcome. Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) which is a known agent of nasal, extranodal NK/T cell lymphoma (ENKTCL) can switch the BAFF activating promoter leading to higher expression of BAFF in EBV-related tumor cells. However, the relationship between BAFF and ENKTCL has not been reported. Here we proposed a hypothesis that BAFF might play a regulatory role in ENKTCL development and maintenance. Our results showed that serum BAFF in ENKTCL patients was significantly higher than that in control group and negatively correlated with patients' survival. It may be a valuable prognostic factor and deserved further study.

Malonyl-CoA synthetase, encoded by ACYL ACTIVATING ENZYME13, is essential for growth and development of Arabidopsis.

Malonyl-CoA is the precursor for fatty acid synthesis and elongation. It is also one of the building blocks for the biosynthesis of some phytoalexins, flavonoids, and many malonylated compounds. In plants as well as in animals, malonyl-CoA is almost exclusively derived from acetyl-CoA by acetyl-CoA carboxylase (EC 6.4.1.2). However, previous studies have suggested that malonyl-CoA may also be made directly from malonic acid by malonyl-CoA synthetase (EC 6.2.1.14). Here, we report the cloning of a eukaryotic malonyl-CoA synthetase gene, Acyl Activating Enzyme13 (AAE13; At3g16170), from Arabidopsis thaliana. Recombinant AAE13 protein showed high activity against malonic acid (K(m) = 529.4 ± 98.5 µM; V(m) = 24.0 ± 2.7 µmol/mg/min) but little or no activity against other dicarboxylic or fatty acids tested. Exogenous malonic acid was toxic to Arabidopsis seedlings and caused accumulation of malonic and succinic acids in the seedlings. aae13 null mutants also grew poorly and accumulated malonic and succinic acids. These defects were complemented by an AAE13 transgene or by a bacterial malonyl-CoA synthetase gene under control of the AAE13 promoter. Our results demonstrate that the malonyl-CoA synthetase encoded by AAE13 is essential for healthy growth and development, probably because it is required for the detoxification of malonate.

Subsets of a large cognitive battery better power clinical trials on early stage Alzheimer's disease.

BACKGROUND/AIMS: Cognitive batteries routinely used by the Alzheimer's disease (AD) research community may contain items that are uninformative for tracking disease progression to power clinical trials on early stage AD. We aim to identify the subsets of the most informative items from an existing cognitive battery to better power clinical trials on early AD. METHODS: Longitudinal change in item scores from the battery was associated with the onset of mild cognitive impairment (MCI) in 1,513 elderly individuals. Items whose longitudinal changes were correlated with the onset of MCI were selected as informative for tracking the early cognitive progression. RESULTS: 226 items in the battery were annually assessed over a follow-up of up to 13 years. Changes of item scores over time from 187 items were significantly correlated with the onset of MCI. For clinical trials on preclinical AD and on MCI, informative items permit smaller or similar sample sizes as compared to the entire battery, whereas uninformative items require much larger sample sizes. CONCLUSIONS: Longitudinal changes in item scores from about 17% of items in the cognitive battery are uninformative for tracking early disease progression. Clinical trials on early AD can be better powered using informative items rather than the entire battery.