Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0•95 (0•911-0•992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET⁺) versus healthy group, and 0•97 (0•924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0•93 (0•876-0•989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker. Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01) to E.C.; Spanish Ministry of Economy and Competitiveness (SAF2017-85310-R) to J.L.C., and (PSI2017-85311-P) to M.A.; International Centre on ageing CENIE-POCTEP (0348_CIE_6_E) to M.A.; Instituto de Salud Carlos III (PIE16/00021, PI17/01799), to H.B.

Kynurenic acid (KYNA) is a product of the tryptophan (TRP) metabolism via the kynurenine pathway (KP). This pathway is activated in neurodegenerative disorders, such as Alzheimer´s disease (AD). KYNA is primarily produced by astrocytes and is considered neuroprotective. Thus, altered KYNA levels may suggest an inflammatory response. Very recently, significant increases in KYNA levels were reported in cerebrospinal fluid (CSF) from AD patients compared with normal controls. In this study, we assessed the accuracy of KYNA in CSF for the classification of patients with AD, cognitively healthy controls, and patients with a variety of other neurodegenerative diseases, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy (PSP). Averaged KYNA concentration in CSF was higher in patients with AD when compared with healthy subjects and with all the other differentially diagnosed groups. There were no significant differences in KYNA levels in CSF between any other neurodegenerative groups and controls. These results suggest a specific increase in KYNA concentration in CSF from AD patients not seen in other neurodegenerative diseases.

Semantic variant primary progressive aphasia (svPPA) is a clinical syndrome included in the frontotemporal dementia (FTD) spectrum. Unlike other forms of FTD, it is sporadic in the majority of cases and not commonly associated with motor neuron disease (MND). We describe a case of svPPA associated with MND in the same family, due to a mutation of the transactive response DNA binding protein (TARDBP) gene, and review the literature.

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.

Dynamic early-phase PET images acquired with radiotracers binding to fibrillar amyloid-beta (Aβ) have shown to correlate with [¹⁸F]fluorodeoxyglucose (FDG) PET images and provide perfusion-like information. Perfusion information of static PET scans acquired during the first minute after radiotracer injection (FMF, first-minute-frame) is compared to [¹⁸F]FDG PET images. FMFs of 60 patients acquired with [¹⁸F]florbetapir (FBP), [¹⁸F]flutemetamol (FMM), and [¹⁸F]florbetaben (FBB) are compared to [¹⁸F]FDG PET images. Regional standardized uptake value ratios (SUVR) are directly compared and intrapatient Pearson’s correlation coefficients are calculated to evaluate the correlation of FMFs to their corresponding [¹⁸F]FDG PET images. Additionally, regional interpatient correlations are calculated. The intensity profiles of mean SUVRs among the study cohort (r = 0.98, p < 0.001) and intrapatient analyses show strong correlations between FMFs and [¹⁸F]FDG PET images (r = 0.93 ± 0.05). Regional VOI-based analyses also result in high correlation coefficients. The FMF shows similar information to the cerebral metabolic patterns obtained by [¹⁸F]FDG PET imaging. Therefore, it could be an alternative to the dynamic imaging of early phase amyloid PET and be used as an additional neurodegeneration biomarker in amyloid PET studies in routine clinical practice while being acquired at the same time as amyloid PET images.

Introduction: Little is known about the relation of cognitive impairment (CI) to COVID-19 mortality. Here, we analyse the frequency of CI in deceased COVID-19 patients. Methods: We included 477 adult cases that died after admission from March 1 to March 31, 2020: 281 with confirmed COVID-19, 58 probable COVID-19, and 138 who died of other causes. Results: The number of comorbidities was high in the confirmed COVID-19, and CI was common (30%: 21.1% dementia; 8.9% mild cognitive impairment). Subjects with CI were older, more lived in nursing homes and had shorter times from symptom onset to death than those without CI. COVID-19 patients with CI were rarely admitted to the ICU and fewer received non-invasive mechanical ventilation, but palliative care was provided more often. Conclusions: Dementia is a frequent comorbidity in COVID-19 deceased patients. The burden of COVID-19 in the dementia community will be high.