Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer’s disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology.

Abstract. Using 2B-CLDCLASS-LIDAR (radar–lidar) cloud classification and 2B-FLXHR-LIDAR radiation products from CloudSat over 4 years, this study evaluates the co-occurrence frequencies of different cloud types, analyzes their along-track horizontal scales and cloud radiative effects (CREs), and utilizes the vertical distributions of cloud types to evaluate cloud-overlap assumptions. The statistical results show that high clouds, altostratus (As), altocumulus (Ac) and cumulus (Cu) tend to coexist with other cloud types. However, stratus (St) (or stratocumulus, Sc), nimbostratus (Ns) and convective clouds are much more likely to exhibit individual features than other cloud types. On average, altostratus-over-stratus/stratocumulus cloud systems have a maximum horizontal scale of 17.4 km, with a standard deviation of 23.5 km. Altocumulus-over-cumulus cloud types have a minimum scale of 2.8 km, with a standard deviation of 3.1 km. By considering the weight of each multilayered cloud type, we find that the global mean instantaneous net CREs of multilayered cloud systems during the daytime are approximately −41.3 and −50.2 W m−2, which account for 40.1 and 42.3% of the global mean total net CREs at the top of the atmosphere (TOA) and at the surface, respectively. The radiative contributions of high-over-altocumulus and high-over-stratus/stratocumulus (or cumulus) in the all multilayered cloud systems are dominant due to their frequency. Considering the overlap of cloud types, the cloud fraction based on the random overlap assumption is underestimated over vast oceans, except in the west-central Pacific Ocean warm pool. Obvious overestimations mainly occur over tropical and subtropical land masses. In view of a lower degree of overlap than that predicted by the random overlap assumption to occur over the vast ocean, particularly poleward of 40° S, the study therefore suggests that a linear combination of minimum and random overlap assumptions may further improve the predictions of actual cloud fractions for multilayered cloud types (e.g., As + St/Sc and Ac + St/Sc) over the Southern Ocean. The establishment of a statistical relationship between multilayered cloud types and the environmental conditions (e.g., atmospheric vertical motion, convective stability and wind shear) would be useful for parameterization design of cloud overlap in numerical models.

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