Luca Cuffaro
On the last day of the congress, the EAN Scientific Panel of dementia and cognitive disorders organized a symposium with the aim to examine the neuropathological features of non-Alzheimer pathology in the elderly.
In the first lecture, Prof. Philip Scheltens from Netherlands, presented “The concept of Suspected non-Alzheimer disease pathophysiology (SNAP) in 2020: does it still survive?”.
At the beginning of his lecture, he explained the ATN classification of CSF biomarkers, based on three principal parameters: beta-amyloid pathology (A), tau pathology (T) and other nonspecific biomarkers of neurodegeneration (N).
The acronym of SNAP has been coined in 2012 and many studies have described extensively this concept from each corner. The prevalence of SNAP is around 20-30% in cognitively healthy subjects and it is around 20-40% in memory clinic patients. In patients with mild cognitive impairment (MCI) SNAP predicts progression with high variable in term of percentage. Moreover, SNAP consists of several pathologies, despite FTD and LATE are quite prevalent. In conclusion, this entity is still effective, even though the scientific community does not use it as term per se, but to refer to a broad group of non-Alzheimer pathophysiologic condition.
The second lecture was “Primary age-related tauopathy: are we able to intercept it?”, presented by Prof. Irina Alafuzoff, from Sweden.
It has been shown data from the broad study conducted by the speaker about the minimal neuropathologic diagnosis for brain banking in the normal middle-age, aged brain and in neurodegenerative disorders. It has been analysed 923 brains with a standardized method of sampling of brain regions and the results have been very interesting: in 14% of cases the HPt (hyperphosphorylated tau) was limited to locus coeruleus; only 8% of subjects with PART (Primary Age-Related tauopathy) have displayed dementia during life, when compared with 29% of subjects in the ADNC (Alzheimer’s disease neuropathologic change). As proposed in the conclusions, there are two differing aging related HPt alterations displaying a neuroanatomical distribution of HPt, as described by Braak and the group with concomitant A-beta pathology (ADNC) have been shown to have higher percentage of dementia symptoms and higher incidence of concurrent and sever TDP43 pathology, compared with that one without concomitant A-beta pathology (PART).
The third lecture have been presented by Prof. Gabor G. Kovacs, from Canada and he give an extensive overview about “Limbic-predominat age-related TDP-43 encephalopathy (LATE)”.
LATE neuropathological change (NC) consists of TDP-43 pathology mostly in amygdala and hippocampus, while is rare in other regions. The Hippocampal Sclerosis (HS), frequently observed in epilepsy-related or hypoxic status, is a pathological feature not always present in LATE-NC, where it appears to have a peculiar anatomic distribution. The author stated that LATE should be used to describe the clinical disease, whereas LATE-NC should be the pathological description, defined by a stereotypical TDP-43 proteinopathy with or without HS. Furthermore, LATE-NC is associated with an amnestic syndrome mimicking Alzheimer’s dementia, so it has significant implications for public health and therapy trials. In conclusion, the development of specific LATE biomarker(s) is a high scientific priority and the relationship/difference to FTLD-TDP should be further examined and defined.
The final lecture has been made by Prof. Dietmar Thal, from Belgium. He discussed about the “Cerebral amyloid angiopathy”.
The Cerebral amyloid angiopathy (CAA) describes a deposition of amyloid (congo-red stained material) in cerebral and/or leptomeningeal blood vessels and several amyloidogenic proteins can concur to develop this condition.
The clinical signs associated to CAA are microbleeds, that are specific sign for CAA at MRI, and lobar hemorrhages, that are suggestive for CAA in the brains of elderly individuals at MRI or CT, while cortical infarcts are not diagnostic for it. From the neuropathological perspective the pathological analysis of resected bleedings is diagnostic for CAA and genetics for APP-Dutch, TTR, PrP, Gelsolin, Abri, Adan, Cystatin C mutations is important diagnostic step to perform. Key points explained from the speaker are: (1) sporadic CAA is associated with AD; (2) APOE e4 allele is a risk factor for capillary CAA in sporadic CAA; (3) Capillary CAA is associated with allocortical microinfarcts in demented individuals and can in so doing increase cognitive decline. It has been made an important highlight on non-Amyloid beta CAA, that is in general a quite rare disease and the most important type is CAA related to transthyretin mutations. Indeed, this last condition can be treated successfully by liver transplantation or TTR stabilizers.
We may conclude that symposium was well accepted and several comments and questions were raised during a lively discussion.
