Tracing of temporo-entorhinal connections in the human brain: cognitively impaired argyrophilic grain disease cases show dendritic alterations but no axonal disconnection of temporo-entorhinal association neurons

Argyrophilic grain disease (AGD), a neurodegenerative disorder, is often associated with mild to moderate Alzheimer’s disease (AD)-related pathology. The development of dementia in AGD is associated with the extent of coexisting AD-related pathology. Therefore, the question arises whether the degenerative changes in the neuronal network of demented AGD-patients represent a distinct pattern or show similar changes of disconnection as considered for AD. We were able to apply DiI-tracing in two human autopsy cases with mild AD-related pathology (controls), in one AD-patient, in one non-demented patient with advanced AD-related pathology, and in three cognitively impaired AGD-patients. DiI-crystals were injected into the entorhinal cortex. Pyramidal neurons of layers III and V of the adjacent temporal neocortex (area 35) were retrogradely marked with the tracer and analyzed. The AD case did not exhibit any retrogradely labeled neurons in the temporal neocortex. In the non-demented case with advanced AD-related pathology, the number of traced neurons was reduced as compared to that in the two controls and in the three AGD cases. In contrast, all three cognitively impaired AGD cases exhibited labeled pyramidal neurons in area 35 in an almost similar number as in the controls. However, alterations in the dendritic tree were observed in the AGD cases. These results show the existence of temporo-entorhinal connections in the adult human brain similar to those reported in animal models. Furthermore, the present study based on seven cases is the first attempt to study changes in the neuronal network in a human tauopathy with targeted axonal tracing techniques. Our findings in three cognitively impaired AGD cases suggest that AGD-related dementia constitutes a distinct disorder with a characteristic pattern of degeneration in the neuronal network

A Blood-Based Screening Tool for Alzheimer's Disease That Spans Serum and Plasma: Findings from TARC and ADNI

There is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer's disease (AD) at the population level.To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma. status) data.Alzheimer's disease.11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49–14.47), the likelihood ratio of not having AD based on the algorithm (LR−) = 3.55 (SE = 1.15; 2.22–5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86–69.47).It is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses

Potential human transmission of amyloid β pathology: surveillance and risks

Studies in experimental animals show transmissibility of amyloidogenic proteins associated with prion diseases, Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Although these data raise potential concerns for public health, convincing evidence for human iatrogenic transmission only exists for prions and amyloid β after systemic injections of contaminated growth hormone extracts or dura mater grafts derived from cadavers. Even though these procedures are now obsolete, some reports raise the possibility of iatrogenic transmission of amyloid β through putatively contaminated neurosurgical equipment. Iatrogenic transmission of amyloid β might lead to amyloid deposition in the brain parenchyma and blood vessel walls, potentially resulting in cerebral amyloid angiopathy after several decades. Cerebral amyloid angiopathy can cause life-threatening brain haemorrhages; yet, there is no proof that the transmission of amyloid β can also lead to Alzheimer's dementia. Large, long-term epidemiological studies and sensitive, cost-efficient tools to detect amyloid are needed to better understand any potential routes of amyloid β transmission and to clarify whether other similar proteopathic seeds, such as tau or α-synuclein, can also be transferred iatrogenically

Small Worlds and Semantic Network Growth in Typical and Late Talkers

Network analysis has demonstrated that systems ranging from social networks to electric power grids often involve a small world structure-with local clustering but global ac cess. Critically, small world structure has also been shown to characterize adult human semantic networks. Moreover, the connectivity pattern of these mature networks is consistent with lexical growth processes in which children add new words to their vocabulary based on the structure of the language-learning environment. However, thus far, there is no direct evidence that a child's individual semantic network structure is associated with their early language learning. Here we show that, while typically developing children's early networks show small world structure as early as 15 months and with as few as 55 words, children with language delay (late talkers) have this structure to a smaller degree. This implicates a maladaptive bias in word acquisition for late talkers, potentially indicating a preference for “oddball” words. The findings provide the first evidence of a link between small-world connectivity and lexical development in individual children

Falls in young, middle-aged and older community dwelling adults: perceived cause, environmental factors and injury

BACKGROUND: Falls in older people have been characterized extensively in the literature, however little has been reported regarding falls in middle-aged and younger adults. The objective of this paper is to describe the perceived cause, environmental influences and resultant injuries of falls in 1497 young (20–45 years), middle-aged (46–65 years) and older (> 65 years) men and women from the Baltimore Longitudinal Study on Aging. METHODS: A descriptive study where participants completed a fall history questionnaire describing the circumstances surrounding falls in the previous two years. RESULTS: The reporting of falls increased with age from 18% in young, to 21% in middle-aged and 35% in older adults, with higher rates in women than men. Ambulation was cited as the cause of the fall most frequently in all gender and age groups. Our population reported a higher percentage of injuries (70.5%) than previous studies. The young group reported injuries most frequently to wrist/hand, knees and ankles; the middle-aged to their knees and the older group to their head and knees. Women reported a higher percentage of injuries in all age groups. CONCLUSION: This is the first study to compare falls in young, middle and older aged men and women. Significant differences were found between the three age groups with respect to number of falls, activities engaged in prior to falling, perceived causes of the fall and where they fell

Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease

status: publishe

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging