**4. Wild-type ATTR (ATTRwt), aka. senile systemic amyloidosis**

Systemic Deposition of ATTRwt is a rather common process associated with aging. Previous studies have reported a prevalence of 12–25% for tissue deposition of ATTRwt in people older than 80 year old [74, 75]. Despite very common prevalence in postmortem and tissue studies, ATTRwt is not a very recognized entity among the community physicians and therefore it is rather underdiagnosed. Patients with ATTRwt typically present with cardiac manifestations, including congestive heart failure, atrial fibrillation and other arrhythmias. ATTRwt is increasingly diagnosed as a cause of heart failure with preserved ejection fraction (HFpEF) [76]. Embolic evens are frequently encountered, mean survival period from the onset of congestive heart failure symptoms is ~75 months [19]. There are differences between fATTR and ATTRwt in the pattern and shape of tissue amyloid deposition [74]. In fATTR deposits are predominantly localized in the pericardium and surrounding muscle fascicles, on the other hand, they have patchy plaque-like shapes and mostly appear inside the ventricular wall in ATTRwt cases. Differences also exist between the shape of deposited amyloid fibrils between fATTR and ATTRwt in electron microscopy: in fATTR, long, straight fibrils are arranged in parallel, whereas short, rigid fibrils with haphazard arrangement are noted in ATTRwt, with endocardial region more involved than epicardium [74]. ATTRwt also involves other organs, often subclinically. In the pathological study by Ueda, et al., amyloid deposits were noted in bladder in 5/6 cases; deposits in the thyroid, pancreas, liver, gallbladder, adrenal gland, and gastrointestinal tract were mainly located in the walls of small arteries [74].
