Biology subjects

Bathini, P.

Publications and source records attributed to Bathini, P..

3 recordsLinked to original sources

bioRxiv2026

Early Binding of Anti-Amyloid Antibodies to CAA Drives Complement Activation, Inflammation and ARIA in Mice

Anti-amyloid antibody treatment for Alzheimers disease is linked to Amyloid-Related Imaging Abnormalities (ARIA), including vasogenic edema (ARIA-E) and microhemorrhages (ARIA-H), especially in ApoE {varepsilon}4/4 carriers. To investigate mechanisms underlying ARIA, we examined the binding and temporal vascular effects of immunization with 3D6, the precursor to the anti-amyloid antibody bapineuzumab, in two aged Alzheimers disease amyloid mouse models. Acutely, 3D6 bound to cerebral amyloid angiopathy (CAA), resulting in C1q binding and classical complement activation. Weekly short-term immunization over 7 weeks resulted in elevated CAA- and plaque-associated complement deposition, red blood cell extravasation and microhemorrhages, and was accompanied by significant transcriptomic changes in genes related to complement, inflammation, vascular dysfunction, and endothelial lipid responses. Longer-term dosing over 13-15 weeks further increased complement deposition and was associated with blood-brain barrier disruption, MMP-9 upregulation, and microhemorrhages, accompanied by reduced amyloid burden and modest CAA clearance. C3 levels correlated with microhemorrhage severity. Perivascular macrophages co-localized with complement-decorated CAA in 3D6-treated mice. These findings implicate complement activation as an early key driver of ARIA and suggest that therapeutic targeting of complement may reduce ARIA risk. O_FIG O_LINKSMALLFIG WIDTH=166 HEIGHT=200 SRC="FIGDIR/small/709591v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@14e1950org.highwire.dtl.DTLVardef@5ffad6org.highwire.dtl.DTLVardef@14d19a5org.highwire.dtl.DTLVardef@ceb5d8_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Integrative genomic approaches to study the barley-Pyrenophora teres interaction

Pyrenophora teres f. teres (Ptt), the causal agent of net-form net blotch in barley, was studied using a bi-parental mapping population (Pop1) of 305 isolates derived from a cross between two isolates with contrasting virulence on barley cultivars Skiff and Prior. QTL analysis identified virulence loci on chromosomes (Chr) 3 and 10 for Skiff, and on Chr 1, 4, and 5 for Prior. Major QTL on Chr 3 and 5 explained 24% and 40% of phenotypic variation, respectively. A second population (Pop2) was developed by crossing two Pop1 isolates, one carrying major QTL on Chr 3 and 5 and one avirulent. Isolates from Pop2 with single QTL were phenotyped across a Prior/Skiff recombinant inbred line population to identify corresponding host susceptibility/resistance loci. Skiff virulence QTL on Chr 3 corresponded to barley Chr 3H and 6H, while Prior virulence QTL on Chr 5 mapped to Chr 6H. RNA expression analysis of virulent and avirulent Pop2 isolates identified five candidate genes linked to the Chr 5 QTL, including two predicted effectors. These findings suggest both gene-for-gene and inverse gene-for-gene interactions in the Ptt-barley pathosystem and advance the understanding of molecular mechanisms underlying host-pathogen specificity.

plant biology↗

bioRxiv2020

Systemic inflammation causes microglial dysfunction with a mixed AD-like pathology.

BackgroundAlzheimers disease (AD) is the primary cause of cognitive deficit in elderly humans. Late-onset AD (LOAD) is sporadic, multifactorial, non-Mendelian accounting at present for 95% of the cases in contrast to the genetic form. Risk factors for sporadic AD include Gene: Environment interactions. There is increasing evidence that lifestyle and environmental stress such as infection and chronic inflammation are underlying culprits of neurodegenerative dementia. Dementias that share or mimic pathological processes of AD include cerebrovascular diseases, Lewy body disease, TDP-43 proteinopathy. To date, very few mouse models reproduce the pathophysiological progression of mixed-vascular-AD, while the majority of studies have employed transgenic animals reproducing the familial form. MethodsWe have re-engineered the Polyinosinic:polycytidylic acid (PolyI:C) sterile infection model in wildtype C57Bl6 mice to obtain chronic low-grade systemic inflammation. We have conducted a cross-sectional analysis of aging PolyI:C and Saline control mice (3 months, 6 months, 9 months and 16 months), taking the hippocampus as a reference brain region, based on its vulnerability, and compared the brain aging phenotype to AD progression in humans with mild AD, severe AD and Controls (CTL), parallely in Vascular dementia (VaD) patient specimens. ResultsWe found that PolyI:C mice display both peripheral and central inflammation with a peak at 6 months, associated with memory deficits. The hippocampus is characterized by a pronounced and progressive tauopathy. In PolyI:C brains, microglia undergo aging-dependent morphological rearrangements progressively adopting a phagocytic phenotype. Transcriptomic analysis reveals a profound change in gene expression over the course of aging, with a peak in differential expression at 9 months. We confirm that the proinflammatory marker Lcn2 is one of the genes with the strongest upregulation in PolyI:C mice upon aging. Validation in brains from patients with increasing severity of AD and VaD shows a reproducibility of some gene targets in vascular dementia specimens rather than AD ones, in which only GFAP is strongly increased at the severe stages. ConclusionsThe PolyI:C model of sterile infection demonstrates that peripheral chronic inflammation is sufficient to cause neuropathological processes resembling a mixed-VaD-AD phenotype, with progressive tau hyperphosphorylation, changes in microglia morphology, astrogliosis and gene reprogramming reflecting increased neuroinflammation, vascular remodeling and the loss of neuronal functionality seen to some extent in humans.

neuroscience↗