Therapeutics against Alzheimer’s disease （AD） have been developed mostly based on “amyloid hypothesis”. However, even though reduction of amyloid beta burden in the brain was successful in a number of human clinical trials, the effect on clinical symptoms has not been confirmed.　Therefore, many pharmaceutical companies are currently trying to identify alternative target molecules other than amyloid beta whose direct role in the upstream of Alzheimer’s disease pathology is now challenged.

　　We have been analyzing AD pathology using the non-biased approach such as comprehensive phosphoproteome analysis, and identified multiple molecules like MARCKS and SRRM2 whose phosphorylation states are changed before extracellular amyloid aggregation appear in the brain of four types of AD mouse model.　Their phosphorylation changes are also confirmed in postmortem brains of human AD patients, suggesting such changes may reflect human AD pathology.

　　Phosphorylation of SRRM2 at Ser1068 that occurs at the early stage of AD, loses binding affinity to a chaperone protein TCP1alpha when it is phosphorylated, suppresses transfer of SRRM2 to the nucleus, and inhibits the function of SRRM2 as a scaffold molecule stabilizing RNA-related proteins.　Moreover, we identify PQBP1, a causative gene for human intellectual disability （ID）, as the molecule that is stabilized by SRRM2 in the nucleus.　PQBP1 is involved in post-transcriptional expression of multiple molecules essential for neuronal synapse function, and the decrease leads to abnormal brain function.　Actually, AD model mice show similar synapse phenotypes to that of PQBP1-linked ID model mice.　Gene therapy of AD model mice with AAV-PQBP1 recovers such synapse phenotypes and resultant cognitive impairment.

　　Collectively, we have confirmed existence of several pathological changes that precede extracellular amyloid aggregation, which should be called as “ultra-early stage pathology of AD”, and developed an unexpected strategy of gene therapy using an ID-causative gene to improve synapse function of AD that targets key molecules at the ultra-early stage of AD.

　　Better understanding of the neural mechanisms underlying human social behaviour and cognition is crucial for clinical interventions for developmental disorders and other psychiatric and neurological conditions, as well as the better understanding of the human brain.　In this review, I will summarise three lines of studies demonstrating that early development of such social orienting is a plastic process and is affected by social communicative experience.　Firstly, we highlight that cultural environment influence the development of social attention from very early in childhood.　Secondly, we present evidence from infants of blind parents to demonstrate that early parent-child interaction could lead to unique development of social attention, adaptive to individual environment.　Finally, we discuss the possible neurocognitive mechanisms underlying such developmental plasticity, and potential implications for the understanding of neurodevelopmental disorders.

　　Auditory agnosia occurs due to lesions in the bilateral primary auditory cortex of the temporal lobes. In adults, it is usually a result of a second episode of cerebral bleeding or infarction in either side of the temporal lobe.　Patients with auditory agnosia cannot differentiate verbal sounds （auditory verbal agnosia） or nonverbal sounds including environmental sounds （nonverbal auditory agnosia）.　Some patients cannot differentiate melody, rhythm, tone or harmony （amusia）.　In general, no inner language abnormality is present in auditory agnosia.

　　In pediatric patients, underlying disease leading to auditory agnosia is different from that in adults.　In children, auditory agnosia may occur rarely as a sequela of Herpes meningoencephalitis, adrenoleukodystrophy （ALD） or Landau Kleffner syndrome （LKS）.　Early lesions in ALD are limited to white matter and damage to the auditory pathway is the responsible lesion of auditory agnosia.　Moreover, LKS is a functional disease without organic brain lesions.　The occurrence of auditory agnosia is far lower in children than in adults. Thus, it is all the more important to arrive promptly at a differential diagnosis and treat auditory agnosia by encouraging speech therapy and multiple-modality support.

　　The human visual system consists of multiple, parallel channels which process different information, and each channel constitutes a set of sequential processes.　Light increments and decrements, motion, stereoscopic depth, color, shape etc. are processed separately and simultaneously.　The optic nerve contains fibers from many types of ganglion cells including two major classes of cells:the midget cells representing 80% of the ganglion cells and constituting the parvocellular （P） pathway, the parasol cells representing 5-8% of the ganglion cells and constituting the magnocellular （M） pathway.　The two systems M and P remain segregated and terminate in separate layers in V1.　Their functional properties also differ.　The M pathway is fast conducting and specialized for processing transient information.　Thus, the M pathway is most sensitive to stimuli with low spatial and high temporal frequencies.　The P pathway is more sensitive to higher spatial and lower temporal frequencies, and processes color information （red/green）.　VEPs’ recording should be tailored to answer specific clinical and/or research questions.　Newly developed techniques that can assess the functions of extrastriate as well as striate cortices are discussed.　Thus, an algorithm of sequential steps to evaluate the various levels of visual processing is proposed and its clinical use revisited.　Accordingly, the possible pathophysiological mechanisms of chromatic sensitive epilepsy, mild cognitive impairment and autism spectrum disorder are discussed in terms of the parallel visual processing.

　　It is well-known that cerebrovascular disorders and dementia increase with aging.　On the other hand, epilepsy increases in elder people, but this fact is not well known.　At the author’s memory clinic, about 1% of cases are diagnosed as epilepsy.　In addition, there are about 5% of cases with inter-ictal epileptiform discharge （IED） on the electroencephalogram, and the presence of IEDs may suggest merger of epilepsy.

　　In elderly-onset epilepsy, seizures rarely begin with convulsion and are difficult to diagnose as epilepsy because they show variety of non-convulsive seizure symptoms.　These various seizure symptoms often include memory impairment, and patients with epilepsy tend to visit for the diagnosis of dementia.　Transient epileptic amnesia is an epilepsy with memory impairment as main symptom and requires differential diagnosis from Alzheimer’s disease.　Dementia with Lewy bodies and temporal lobe epilepsy have similar symptoms and require differential diagnosis.

　　Cognitive function often improves when anti-epileptic drugs treatment is given to patients with IED.　We report the results of investigations conducted on 50 cases with IED.　On the other hand, dementia and epilepsy may coexist.　Here we introduce a study suggesting that these two diseases may affect the onset and course of the diseases each other.

　　In this study, we aimed to clarify the relationship between the legibility of handwriting and the characteristics of the developmental disorders （ADHD and （ADHD and ASD）.　Previous studies on fluency and accuracy of reading have revealed that phonological awareness and visual cognition affect reading and writing;however, the relationship between character formation and characteristics of the developmental disorders, ADHD and ASD, has not been fully clarified.　Nine typically developing children and ten children with either ADHD or ASD participated in the present study.　We quantitatively assessed the legibility of the hiragana words that were first listened to and then written down by both groups of children;then, we analyzed the relationship of the legibility of handwriting with the characteristics of the developmental disorders.　Results revealed that children with developmental disorders showed lower legibility scores than typically developing children （p <.0001）.　A negative correlation between inattention and legibility scores in boys with developmental disorders was also demonstrated （r = −0.74, p =.038）.　These results suggest that it is possible to evaluate the characteristics of children with the developmental disorders, ADHD and ASD, by assessing the legibility of handwriting.