CN individuals who are Aβ-positive and have stable longitudinal memory performance may represent the group of asymptomatic AD or may not have reached a threshold of pathology where memory decline is evident.
Indeed, many pathological mutations may only be conditionally pathogenic, exerting a detrimental effect only if and when the genetic and external environments interact to push the phenotype over some notional threshold into pathology.
These results correspond with those of previous studies [4, 13], in which small differences in maximum tumour diameter between an adaptive threshold method and pathology were reported [13], as well as good correlation between maximum diameters obtained from a percentage threshold-based method and pathology [4].
No overt phenotype was observed in the KIKO mice, suggesting that the transcriptional decrease does not reach the critical frataxin threshold required to induce pathology.
In contrast, heterozygous LGI1+/− littermates displayed no spontaneous behavioural epileptic seizures, but auditory stimuli induced seizures at a lower threshold, reflecting the human pathology of sound-triggered seizures in some patients.
Items are rated on a three point scale: 0=pathology absent, 1=some pathology, sub-threshold, and 2=significant to severe pathology.
One way of looking at this seemingly paradoxical observation is that cerebrovascular pathology lowers the threshold for incipient AD pathology to become unmasked as a clinical dementia as has been suggested elsewhere [ 10].
The awareness of distress was the starting point of a process through which distress was constructed as a problem, which implied crossing the threshold from "normal" depression to pathology (see Additional file 1: Appendix 3, point 3.1).
It is plausible that elevated adiposity could increase the risk of dementia through cerebrovascular disease, decreasing the threshold for manifestation of AD pathology, or directly by affecting the accumulation of amyloid or neurodegenerative processes in the brain, the culprit of AD [ 12].
For example, biological phenomena involving thresholds, bursting rhythm models in pathology, optimal control of economic systems, frequency-modulated signal processing systems do exhibit impulse effects.
