Plasma amyloid-β ratios in autosomal dominant Alzheimer's disease: the influence of genotype.

In vitro studies of autosomal dominant Alzheimer's disease implicate longer amyloid-β peptides in disease pathogenesis; however, less is known about the behaviour of these mutations in vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from individuals who were at risk of inheriting a mutation or were symptomatic. We tested for differences in amyloid-β (Aβ)42:38, Aβ42:40 and Aβ38:40 ratios between presenilin 1 (PSEN1) and amyloid precursor protein (APP) carriers. We examined the relationship between plasma and in vitro models of amyloid-β processing and tested for associations with parental age at onset. Thirty-nine participants were mutation carriers (28 PSEN1 and 11 APP). Age- and sex-adjusted models showed marked differences in plasma amyloid-β between genotypes: higher Aβ42:38 in PSEN1 versus APP (P < 0.001) and non-carriers (P < 0.001); higher Aβ38:40 in APP versus PSEN1 (P < 0.001) and non-carriers (P < 0.001); while Aβ42:40 was higher in both mutation groups compared to non-carriers (both P < 0.001). Amyloid-β profiles were reasonably consistent in plasma and cell lines. Within the PSEN1 group, models demonstrated associations between Aβ42:38, Aβ42:40 and Aβ38:40 ratios and parental age at onset. In vivo differences in amyloid-β processing between PSEN1 and APP carriers provide insights into disease pathophysiology, which can inform therapy development

Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study.

Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer's disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house single molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from actual onset in a symptomatic subgroup. In addition, we studied associations between p-tau181 and clinical severity, as well testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO -9.6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p < 0.001) and presymptomatic mutation carriers (p < 0.001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0.93 [95% CI 0.85-0.98]) and presymptomatic (EYO ≥ -7 years) (AUC 0.86 [95% CI 0.72-0.94]) carriers from non-carriers of the same age and sex. From a fitted model there was evidence (p = 0.050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology

Fossil angiosperm wood: its role in the reconstruction of biodiversity and palaeoenvironment

Fossil wood is subject to different taphonomic, sampling and recognition biases in the palaeobotanical record when compared with leaves and palynomorphs. Wood therefore provides a systematically independent source of information that can increase our knowledge of past biodiversity and environments. Increase in fossil wood records from Cretaceous and Tertiary sediments helps further the understanding of trends in anatomical specialization through geological time. These data can then be used to distinguish such specialization from anatomical response to environmental change. Two case studies, a Late Cretaceous early Tertian’ wood flora from Antarctica and a lower Tertiary w ood flora from southern England, have been used to exemplify the importance of studying the fossil wood component of palaeofloras

Fossil woods from Williams Point Beds, Livingston Island, Antarctica: a Late Cretaceous southern high latitude flora

The wood flora from Williams Point, Livingston Island, contains 12 wood types of gymnosperm and angiosperm origin. Recent collections of material have increased the biodiversity of a postulated species-rich vegetation. The gymnosperm wood can be readily assigned to four form-genera: Araucarioxylon Kraus, Araucariopitys Jeffrey, Podocarpoxylon Gothan and Sahnioxylon Bose and Sah. This indicates a diversity of coniferous araucarian and podocarp trees alongside woods of uncertain affinity (Sahnioxylon; Bennettitales). Two angiosperm morphotypes are assigned to the organ genera Hedycaryoxylon Su¨ss (Monimiaceae) and Weinmannioxylon Petriella (Cunoniaceae). The remaining four taxa of angiosperm wood cannot be confidently placed in extant families as they exhibit features that suggest relationships with the Magnoliidae, Hamamelidae and Rosidae. This paper presents the first comprehensive taxonomic revision of the wood flora from Livingston Island and discusses the palaeoecology that prevailed at a latitude of about 60 degrees south during the Late Cretaceous. Newly described taxa are Araucarioxylon chapmanae sp. nov., Araucariopitys antarcticus sp. nov., Podocarpoxylon chapmanae sp. nov., P. verticalis sp. nov., P. communis sp. nov., Weinmannioxylon ackamoides sp. nov., Antarctoxylon livingstonensis gen. et sp. nov., A. multiseriatum gen. et sp. nov., A. heteroporosum gen. et sp. nov. and A. uniperforatum gen et sp. nov

Reconstruction of Antarctic palaeoclimates using angiosperm wood anatomy

Fossil angiosperm wood is abundant within Cretaceous and Tertiary sediments on the Antarctic Peninsula. The wood, which represents the trunks and branches of large forest trees that once grew on an emergent volcanic arc, is exquisitely preserved by petrifaction with calcite and silica. Microscopic anatomical details of the angiosperm wood, such as the intervessel and vessel- ray pitting, are present which has permitted comparison with the anatomy of modern woods and identification of the fossil wood taxa plus investigation of the climate significance of certain anatomical features. The families Nothofagaceae, Monimiaceae, Winteraceae, Illiciaceae and Atherospermataceae have been identified so far. Growth ring analysis indicates that these trees grew well under a favourable temperate climate during both the Late Cretaceous and Early Tertiary. Studies of anatomical features show that some characters, such as vessel diameter and distinctness of growth rings, correlate with changing temperatures and water availability

A new Eocene Araucaria from Seymour Island, Antarctica: evidence from growth form and bark morphology

Araucarian conifers are an important component of Cretaceous through Paleogene floras in the Antarctic Pensinsula. A well-preserved Eocene petrified trunk from Seymour Island, Antarctica reveals the growth form and bark morphology that, along with wood anatomical characteristics, places the tree within Araucaria. The tree was at least 14 m tall with a monopodial habit and horizontally wrinkled bark. Wood-decaying fungi colonized the trunk after it had fallen to the forest floor. The fungi invaded the trunk through the pith and initially along ray cells leaving strongly lignitized cells relatively intact. This indicates preferentially consumption of sugars suggesting these fungi formed the first stages of nutrient recycling within this Eocene ecosystem

Cretaceous patterns of floristic change in the Antarctic Peninsula

Cretaceous radiation of angiosperms from low to high palaeolatitudes, coupled with the break-up of Gondwana, played a major role in establishing and maintaining biogeographic patterns across the southern hemisphere. Uncertainties in details of plate reconstructions provide conflicting hypotheses about area relationships of Gondwana fragments. This has led to a number of competing proposals concerning angiosperm migration across Gondwana. Central to this debate is the role of the Antarctic Peninsula, a region that is often envisaged as providing the main connection between east and west Gondwana. The initial radiation of angiosperms into the Antarctic Peninsula region, however, postdates appearances elsewhere in east Gondwana (e.g. Australia), strongly suggesting that the Antarctic Peninsula was not the main gateway, at least in the early stages of Gondwana radiation. A steep climatic gradient in this part of the world probably acted as an effective barrier to angiosperm radiation. The peak of floristic replacement coincides with the peak of Cretaceous warmth (Turonian) which in turn suggests that climatic warming acted as a forcing mechanism by pushing latitudinal belts of vegetation southwards. Once into the southern high latitudes angiosperms diversified, and as climates cooled during the Late Cretaceous a number of important groups seem to have their origins here. Recent investigations of Antarctic macro- and microfloras indicate progressive floristic replacement through the Cretaceous. Bryophytes, hepatophytes, bennettites and other seed plants all show a rapid decline in diversity. In contrast, ferns initially decline then recover, while conifers remain relatively stable. The ecological preferences of the replaced groups imply that angiosperms initially occupied areas of disturbance and were understorey colonizers, only later replacing fern thickets and becoming important in the overstorey. This pattern is consistent with those observed elsewhere through the Cretaceous

The first record of fossil atherospermataceous wood from the upper Cretaceous of Antarctica

Fossil wood of the Atherospermataceae from the upper Cretaceous of James Ross Island, Antarctica, is described for the first time and represents the earliest record of this family in the Southern Hemisphere. The specimens are characterised by diffuse porous arrangement of vessels, scalariform perforation plates, scalariform and opposite intervessel pitting and predominantly multiseriate rays which occasionally bear low, uniseriate margins. Despite anatomical conformity at the familial level, the fossil woods are not identical to any one extant genus and have therefore been assigned to the fossil organ genus, Laurelites Nishida, Nishida et Nasa, with which the fossils show greatest similarity