Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios

INTRODUCTION: We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ42 alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration. METHODS: Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ42, Aβ40, and Aβ38 peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay. Data were analyzed using mixed models in R. RESULTS: Decrease of measurable Aβ peptide concentrations was exaggerated in longer peptides, affecting the Aβ42:Aβ40 and Aβ42:Aβ38 ratios. However, the effect size of surface treatment was reduced in Aβ peptide ratios versus Aβ42 alone. For Aβ42:Aβ40, the effect was reduced by approximately 50% (volume) and 75% (transfer) as compared to Aβ42 alone. DISCUSSION: Use of Aβ ratios, in conjunction with concentrations, may mitigate confounding factors and assist the clinical diagnostic process for Alzheimer's disease

Pseudogap in 1d revisited

Two decades ago, Sadovskii found an exact solution of a model describing a pseudogap in electron energy spectrum (first introduced by Lee, Rice and Anderson). The discovery of a pseudogap in high-Tc superconductors has revived the interest to his exact solution. I review the model with the emphasis on physical content, point out an error in the original Sadovskii's solution and explain which problem he actually solved. A recent incorporation of Sadovskii's ideas into a description of "hot spots" on the Fermi surface in cuprate superconductors (Schmalian, Pines and Stojkovic) is briefly discussed.Comment: Final version to appear in PR

Incommensurate Charge Density Waves in the adiabatic Hubbard-Holstein model

The adiabatic, Holstein-Hubbard model describes electrons on a chain with step $a$ interacting with themselves (with coupling $U$) and with a classical phonon field \f_x (with coupling \l). There is Peierls instability if the electronic ground state energy F(\f) as a functional of \f_x has a minimum which corresponds to a periodic function with period ${\pi\over p_F}$, where $p_F$ is the Fermi momentum. We consider ${p_F\over\pi a}$ irrational so that the CDW is {\it incommensurate} with the chain. We prove in a rigorous way in the spinless case, when \l,U are small and {U\over\l} large, that a)when the electronic interaction is attractive $U<0$ there is no Peierls instability b)when the interaction is repulsive $U>0$ there is Peierls instability in the sense that our convergent expansion for F(\f), truncated at the second order, has a minimum which corresponds to an analytical and ${\pi\over p_F}$ periodic \f_x. Such a minimum is found solving an infinite set of coupled self-consistent equations, one for each of the infinite Fourier modes of \f_x.Comment: 16 pages, 1 picture. To appear Phys. Rev.

Strong damping of phononic heat current by magnetic excitations in SrCu_2(BO_3)_2

Measurements of the thermal conductivity as a function of temperature and magnetic field in the 2D dimer spin system SrCu$_2$(BO$_3$)$_2$ are presented. In zero magnetic field the thermal conductivity along and perpendicular to the magnetic planes shows a pronounced double-peak structure as a function of temperature. The low-temperature maximum is drastically suppressed with increasing magnetic field. Our quantitative analysis reveals that the heat current is due to phonons and that the double-peak structure arises from pronounced resonant scattering of phonons by magnetic excitations.Comment: a bit more than 4 pages, 2 figures included; minor changes to improve the clarity of the presentatio

Genetic Variants and Related Biomarkers in Sporadic Alzheimer's Disease.

From a neuropathological perspective, elderly patients who die with a clinical diagnosis of sporadic Alzheimer's disease (AD) are a heterogeneous group with several different pathologies contributing to the AD phenotype. This poses a challenge when searching for low effect size susceptibility genes for AD. Further, control groups may be contaminated by significant numbers of preclinical AD patients, which also reduces the power of genetic association studies. Here, we discuss how cerebrospinal fluid and imaging biomarkers can be used to increase the chance of finding novel susceptibility genes and as a means to study the functional consequences of risk alleles

Ginzburg-Landau theory of phase transitions in quasi-one-dimensional systems

A wide range of quasi-one-dimensional materials, consisting of weakly coupled chains, undergo three-dimensional phase transitions that can be described by a complex order parameter. A Ginzburg-Landau theory is derived for such a transition. It is shown that intrachain fluctuations in the order parameter play a crucial role and must be treated exactly. The effect of these fluctuations is determined by a single dimensionless parameter. The three-dimensional transition temperature, the associated specific heat jump, coherence lengths, and width of the critical region, are computed assuming that the single chain Ginzburg-Landau coefficients are independent of temperature. The width of the critical region, estimated from the Ginzburg criterion, is virtually parameter independent, being about 5-8 per cent of the transition temperature. To appear in {\it Physical Review B,} March 1, 1995.Comment: 15 pages, RevTeX, 5 figures in uuencoded compressed tar file

Cerebrospinal fluid metallomics in cerebral amyloid angiopathy: an exploratory analysis.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is associated with symptomatic intracerebral haemorrhage. Biomarkers of clinically silent bleeding events, such as cerebrospinal fluid (CSF) ferritin and iron, might provide novel measures of disease presence and severity. METHODS: We performed an exploratory study comparing CSF iron, ferritin, and other metal levels in patients with CAA, control subjects (CS) and patients with Alzheimer's disease (AD). Ferritin was measured using a latex fixation test; metal analyses were performed using inductively coupled plasma mass spectrometry. RESULTS: CAA patients (n = 10) had higher levels of CSF iron than the AD (n = 20) and CS (n = 10) groups (medians 23.42, 15.48 and 17.71 μg/L, respectively, p = 0.0015); the difference between CAA and AD groups was significant in unadjusted and age-adjusted analyses. We observed a difference in CSF ferritin (medians 10.10, 7.77 and 8.01 ng/ml, for CAA, AD and CS groups, respectively, p = 0.01); the difference between the CAA and AD groups was significant in unadjusted, but not age-adjusted, analyses. We also observed differences between the CAA and AD groups in CSF nickel and cobalt (unadjusted analyses). CONCLUSIONS: In this exploratory study, we provide preliminary evidence for a distinct CSF metallomic profile in patients with CAA. Replication and validation of these results in larger cohorts is needed

Cerebrospinal fluid biomarkers in cerebral amyloid angiopathy

BACKGROUND: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA). OBJECTIVE: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA. METHODS: We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer’s disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service. RESULTS: We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ_{38}, Aβ_{40}, Aβ_{42}, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ_{38}, Aβ_{40}, Aβ_{42}, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ_{42}, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an “AD-like” profile. CONCLUSION: CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed

Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin

After subarachnoid haemorrhage, prolonged exposure to toxic extracellular haemoglobin occurs in the brain. Here, we investigate the role of haemoglobin neurotoxicity in vivo and its prevention. In humans after subarachnoid haemorrhage, haemoglobin in cerebrospinal fluid was associated with neurofilament light chain, a marker of neuronal damage. Most haemoglobin was not complexed with haptoglobin, an endogenous haemoglobin scavenger present at very low concentration in the brain. Exogenously added haptoglobin bound most uncomplexed haemoglobin, in the first 2 weeks after human subarachnoid haemorrhage, indicating a wide therapeutic window. In mice, the behavioural, vascular, cellular and molecular changes seen after human subarachnoid haemorrhage were recapitulated by modelling a single aspect of subarachnoid haemorrhage: prolonged intrathecal exposure to haemoglobin. Haemoglobin-induced behavioural deficits and astrocytic, microglial and synaptic changes were attenuated by haptoglobin. Haptoglobin treatment did not attenuate large-vessel vasospasm, yet improved clinical outcome by restricting diffusion of haemoglobin into the parenchyma and reducing small-vessel vasospasm. In summary, haemoglobin toxicity is of clinical importance and preventable by haptoglobin, independent of large-vessel vasospasm

Older persons’ experiences of Reflective STRENGTH‐Giving Dialogues – ‘It\u27s a push to move forward’

Rationale: Experiences of the innovative method Reflective STRENGTH‐Giving Dialogue (STRENGTH), which is grounded in a lifeworld perspective and developed to improve quality of care, is described in this study. Innovative thinking in developing health and social care, which may include digital solutions, is required to ensure a meaningful and dignified life in old age. Aim: The aim of this study was to describe experiences of the intervention Reflective STRENGTH‐Giving Dialogue from the perspective of older persons living with long‐term health problems. Method: Individual qualitative interviews were conducted with 27 older persons who participated in the intervention. The older persons wrote notes from each dialogue in booklets, and the booklets became part of the study data, analysed with a Reflective Lifeworld Research approach. Results: STRENGTH is experienced as an opportunity to reflect upon life and identify small and large life projects. Dialogues that lead to change in thoughts and actions influence the older persons\u27 well‐being, sense of balance, joy and meaning in life. There is an experience of STRENGTH as a starting point and a push to move forward in an effort to experience joy and meaning in life when living with long‐term health problems. Conclusions: STRENGTH has the potential to contribute to quality improvement in person‐centred care and enhance meaning in life for older persons living with long‐term health problems. However, the use of a digital tool in this particular context poses challenges that must be considered