**7. Impact of the ECM in old age on memory function and cognitive integrity**

With respect to age, the importance to provide profound tenacity to conserve experience-based memories might increase over the life span. Deficits or malfunctions of several ECM molecules or ECM-chopping enzymes can affect cognitive and psychological conditions. For instance, in humans neurotrypsin has been identified as essential component for cognitive functions. Deficits in the neurotrypsin genotype have been correlated with severe mental retardation [46]. Further, Cichon et al. [47] reported a genetic variation of neurocan as susceptibility factor for bipolar disorders. With relation to ageing, hippocampal ECM levels have been suggested to show an age-dependent increase conquering age-related cognitive decline. In this line, the Alzheimer's disease (AD) mouse model APP/PS1 showed a significant upregulation of several matrix components correlating with impairments in hippocampal LTP and contextual memory [48]. Intra-hippocampal injections of chABC restored both [48] suggesting an important, but yet elusive role for the ECM in early memory impairment in AD, as the mere correlative findings about ECM alterations in dementia are highly controversial and are far from conclu‐ sive [33]. That these data might have relevant impacts for human AD is indicated by findings of correlating HA levels in the cerebrospinal fluid of female AD patients and particular ADrelated biomarkers [49]. Further, MMP9 levels have been found to be increased in Alzheimer patients [50] and to cleave the amyloid beta peptide leading to AD-typical neuritic plaques [51]. Its role in Aβ-induced cognitive decline is however elusive [52].
